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Interactions between Muscle and Bone—Where Physics Meets Biology
Open accessAbstract
Muscle and bone interact via physical forces and secreted osteokines and myokines. Physical forces are generated through gravity, locomotion, exercise, and external devices. Cells sense mechanical strain via adhesion molecules and translate it into biochemical responses, modulating the basic mechanisms of cellular biology such as lineage commitment, tissue formation, and maturation. This may result in the initiation of bone formation, muscle hypertrophy, and the enhanced production of extracellular matrix constituents, adhesion molecules, and cytoskeletal elements. Bone and muscle mass, resistance to strain, and the stiffness of matrix, cells, and tissues are enhanced, influencing fracture resistance and muscle power. This propagates a dynamic and continuous reciprocity of physicochemical interaction. Secreted growth and differentiation factors are important effectors of mutual interaction. The acute effects of exercise induce the secretion of exosomes with cargo molecules that are capable of mediating the endocrine effects between muscle, bone, and the organism. Long-term changes induce adaptations of the respective tissue secretome that maintain adequate homeostatic conditions. Lessons from unloading, microgravity, and disuse teach us that gratuitous tissue is removed or reorganized while immobility and inflammation trigger muscle and bone marrow fatty infiltration and propagate degenerative diseases such as sarcopenia and osteoporosis. Ongoing research will certainly find new therapeutic targets for prevention and treatment.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
This review synthesizes how muscle and bone communicate through mechanical forces and secreted factors, integrating mechanobiology with endocrine/paracrine signaling. It argues that loading maintains musculoskeletal homeostasis while unloading and chronic inflammation drive fatty infiltration and degenerative diseases such as sarcopenia and osteoporosis.
Key findings
- Mechanical impacts ranging from 0.1 to 100 kPa are sensed by adhesion molecules, ion channels, the primary cilium, and other mechanotransduction machinery, leading to bone formation, muscle hypertrophy, and enhanced ECM/cytoskeletal stiffness, fracture resistance, and muscle power.
- Muscle and bone act as endocrine organs via myokines/osteokines and extracellular vesicles; exosomes are 50–150 nm and microvesicles 50–1000 nm (up to 10 µm), carrying miRNA, proteins, and organelles that may mediate exercise-induced cross-talk.
- Unloading causes rapid loss: a meta-analysis of 75 simulated microgravity studies found moderate muscle changes within 7–14 days and large effects on muscle force, mass, and peak power after 35 days; 90-day 6° head-down tilt bed rest decreased muscle fiber cross-sectional area by 26%, with increased SOST and myostatin that was reversible upon reloading.
- Chronic inflammation and disuse promote muscle fatty infiltration and bone marrow adipose expansion; in the EFFECT study of 40 female acute hip fracture patients and 55 controls, soft tissue parameters discriminated hip fractures as well as trabecular BMD plus cortical thickness.
Methods
- Narrative review; no primary experimental data are reported. It synthesizes mechanistic, developmental, clinical, imaging, and spaceflight/bed-rest literature.
- Cites specific studies and meta-analyses, including 75 simulated microgravity studies, a 90-day bed-rest study, the EFFECT cross-sectional study of 40 female hip fracture patients and 55 controls, and imaging methods such as DXA, BIA, CT, MRI/Dixon, and MRS.
- Main analysis is conceptual integration of mechanotransduction, secretome/extracellular vesicle biology, immune and endothelial interactions, epigenetics, and disease mechanisms.
Limitations
- The paper states that more research is needed to dissect molecular events, define the borders between beneficial and harmful mechanical stimuli, and understand exercise resistance in disease; it also says it cannot provide an in-depth review of any pathology.
- Evident from the text: as a narrative review, no systematic search strategy or risk-of-bias assessment is described, and conclusions rely on selected cited literature rather than new data.
- Evident from the text: many mechanistic claims derive from mouse or in vitro studies and are not fully validated in humans; imaging lacks guidelines for which parameters to quantify, and direct comparison of CT muscle density with MRI Dixon fat fraction has not been published.
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Figures
![Figure 2 Mechanisms of mechanotransduction. Graphical summary of the current knowledge on the transduction of mechanical signals into a cellular response. A) Mechanical strain applied to the cell and (the resulting) fluid flow activate receptors and channels and their downstream signaling cascades. In a tissue context, strain is transmitted between cells via a series of adhesion molecules such as integrins, cadherins, and tight junctions. Transcription factors become nucleotropic and address DNA regulatory elements such as repressors, enhancers, and their specific DNA response elements. Adaptive transcription and translation are initiated and lead to changes in transcriptome, proteome, and especially the secretome to communicate with neighbors and distant tissues. The expression and secretion of extracellular matrix proteins as parts of the secretome are upregulated. As a consequence, the incoming forces and the resistive response to external forces are enhanced, and a new homeostasis situation is produced. Similarly, the production of proteins of the cytoskeleton is enhanced, the cytoskeleton is also becoming stiffer, and the contractile proteins generate even more active forces. B) Fluid flow is sensed by the primary cilium. The relevant structural features of a primary cilium are schematically depicted on the right side, while the signaling cascades and tools for mechanotransduction are depicted on the left side. Deflection of the cilium generates signaling [43,44]. Intraflagellar transport is a means of active transport of signaling peptides to and from the cell body. C) The constitutive secretory pathway and the regulated secretory pathway are schematically depicted. While the latter has not been demonstrated in muscle or bone, it is characteristic for truly endocrine cells and requires complex sorting and the intravesicular storage of preformed proteins that are extruded upon endocrine signals. The constitutive pathway requires characteristic secretory peptide sequences to be continuously released into the extracellular environment and subsequently the circulation. The release of vesicles upon exercise-related calcium flux into the cell has been demonstrated to be a candidate mechanism for the release of proteins and miRNAs. Abbreviations: RTK: receptor tyrosine kinase; GPCR: G-protein coupled receptor; ATP: adenosine triphosphate; cAMP: cyclic adenosine-monophosphate; ECM: extracellular matrix; AKAPs: A-kinase anchoring proteins; PDEs: phosphodiesterases; P2X7R: purinergic receptor P2X, ligand-gated ion channel; TGN: trans-Golgi-network; This figures was created using inspiring information and cartoons from [6,9,40,44,45,46,47,48,49,50,51].](/paper-figures/86bea58ebf894f4986cad05e8231fc1f/interactions-between-muscle-and-bonewhere-physics-meets-biology-figure-2.jpg)
Verification
Claims the paper makes
102 Not checked yet · 24 Own interpretation · 19 No basis given
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In the paper
“Many interactions are not only bilateral but follow a multilateral or even organismic relationship, involving metabolism and the nervous system (Figure 1).”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 1. Introduction
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In the paper
“The acute effects of exercise induce the secretion of exosomes with cargo molecules that are capable of mediating the endocrine effects between muscle, bone, and the organism.”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > Abstract
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In the paper
“Cells sense mechanical strain via adhesion molecules and translate it into biochemical responses, modulating the basic mechanisms of cellular biology such as lineage commitment, tissue formation, and maturation.”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Lessons from unloading, microgravity, and disuse teach us that gratuitous tissue is removed or reorganized”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Secreted growth and differentiation factors are important effectors of mutual interaction.”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > Abstract
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In the paper
“Muscle and bone interact via physical forces and secreted osteokines and myokines.”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > Abstract
What the sources say
- Not checked yetcites [1] Felsenthal, 2017, Mechanical regulation of musculoskeletal system development, Dev. source
- Not checked yetcites [2] Mikolajewicz, 2019, Transmission of Mechanical Information by Purinergic Signaling, Biophys. J. source
- Not checked yetcites [3] Vogel, 2018, Unraveling the Mechanobiology of Extracellular Matrix, Annu. Rev. Physiol. source
- Not checked yetcites [4] Ayad, 2019, Tissue mechanics, an important regulator of development and disease, Philos. Trans. R. Soc. B: Boil. Sci. source
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In the paper
“and propagate degenerative diseases such as sarcopenia and osteoporosis.”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > Abstract
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In the paper
“Recent information indicates that the reciprocity of mechanochemical interaction is extremely dynamic, including the cellular, the tissue, and the organismic level [1,2,3,4].”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 1. Introduction
What the sources say
- Not checked yetcites [1] Felsenthal, 2017, Mechanical regulation of musculoskeletal system development, Dev. source
- Not checked yetcites [2] Mikolajewicz, 2019, Transmission of Mechanical Information by Purinergic Signaling, Biophys. J. source
- Not checked yetcites [3] Vogel, 2018, Unraveling the Mechanobiology of Extracellular Matrix, Annu. Rev. Physiol. source
- Not checked yetcites [4] Ayad, 2019, Tissue mechanics, an important regulator of development and disease, Philos. Trans. R. Soc. B: Boil. Sci. source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“The physical forces generated in the context of motion are extremely variable from very low to high impact.”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 2. Principles of Interaction between Muscle and Bone > 2.1. Physical Forces
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In the paper
“Connective tissues physically joining muscle and bone, especially tendons and ligaments, naturally play a critical role in this interaction, as addressed in a recent review article in detail [5].”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 1. Introduction
What the sources say
- Not checked yetcites [5] Nassari, 2017, Non-myogenic Contribution to Muscle Development and Homeostasis: The Role of Connective Tissues, Front. Cell Dev. Boil.
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In the paper
“After adjustment for BMD and cortical thickness, the hip fracture group was characterized by the lower relative adipose tissue volume of the upper thigh and some of the texture parameters discriminated the osteoporotic hip fracture [204].”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 4. Muscle and Bone Interactions in Disease—Lessons and Backflashes from Pathology > 4.2. Inflammation and Fatty Degeneration—Lessons from Imaging and Structural Analyses
What the sources say
- Not checked yetcites [204] Museyko, 2019, Three-dimensional Distribution of Muscle and Adipose Tissue of the Thigh at CT: Association with Acute Hip Fracture, Radiol. source
plaincorrelationaln = 40- Asserted: passes — The authors put it forward as true.
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In the paper
“Physical forces are generated through gravity, locomotion, exercise, and external devices.”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > Abstract
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In the paper
“This may result in the initiation of bone formation, muscle hypertrophy, and the enhanced production of extracellular matrix constituents, adhesion molecules, and cytoskeletal elements.”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > Abstract
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“immobility and inflammation trigger muscle and bone marrow fatty infiltration”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Bone and muscle mass, resistance to strain, and the stiffness of matrix, cells, and tissues are enhanced, influencing fracture resistance and muscle power.”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The former prevail in muscle while bone strongly (but not exclusively) responds to fluid flow in the osteocyte canalicular network [9].”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 2. Principles of Interaction between Muscle and Bone > 2.1. Physical Forces
What the sources say
- Not checked yetcites [9] Nachury, 2019, Establishing and regulating the composition of cilia for signal transduction, Nat. Rev. Mol. Cell Boil. source
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In the paper
““virtually every step of cell and tissue biology depends upon mechanochemical events””
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 2. Principles of Interaction between Muscle and Bone > 2.1. Physical Forces
What the sources say
- Not checked yetcites [18] Storm, 2017, Mechanoreciprocity in cell migration, Nat.
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In the paper
“The clinical result of physical impact is high bone and muscle mass, resulting in enhanced fracture resistance and muscle power (see also Figure 2A,B).”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 2. Principles of Interaction between Muscle and Bone > 2.1. Physical Forces
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In the paper
“Mechanical stimuli can be transmitted through deformation (stretching and compression) and/or shear strain applied by fluids that pass by.”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 2. Principles of Interaction between Muscle and Bone > 2.1. Physical Forces
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In the paper
“There is no doubt that external mechanical vibration may variably substitute for gravity and add up to active muscle contraction both in space missions and as dedicated types of exercise.”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 2. Principles of Interaction between Muscle and Bone > 2.1. Physical Forces
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In the paper
“In human myoblasts, Cav3 deficiency was associated with the hyperactivation of IL-6-STAT3 signaling (interleukin-6, signal transducer and activator of transcription 3), which is a pathway that in the presence of WT Cav3 turned out to be regulated by mechanical strain in a Cav3-dependent manner [35].”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 2. Principles of Interaction between Muscle and Bone > 2.1. Physical Forces
What the sources say
- Not checked yetcites [35] Dewulf, 2019, Dystrophy-associated caveolin-3 mutations reveal that caveolae couple IL6/STAT3 signaling with mechanosensing in human muscle cells, Nat. Commun. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Mechanical bending/deflection of the cilium was reported to enhance prostaglandin-endoperoxide synthase 2 (PTGS2 alias COX2) expression and prostaglandin production as well as bone morphogenetic protein 2 (BMP 2) and osteopontin expression.”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 2. Principles of Interaction between Muscle and Bone > 2.1. Physical Forces
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Secreted proteins and signaling molecules are the basis of mutual interaction between muscle and bone both in a paracrine and also an endocrine setting.”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 2. Principles of Interaction between Muscle and Bone > 2.2. Systemic Mutual Interactions of Skeletal Muscle and Bone
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In muscle, mechanosensing is mainly transduced via deformation strains, but still, the primary cilium has been related to satellite cell self-renewal and muscle cell differentiation in mice [42].”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 2. Principles of Interaction between Muscle and Bone > 2.1. Physical Forces
What the sources say
- Not checked yetcites [42] Marican, 2016, Asymmetric Distribution of Primary Cilia Allocates Satellite Cells for Self-Renewal, Stem Cell Rep. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“The primary cilium is a unique subcellular organelle composed of nine (+0) axonema structures (Figure 2B).”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 2. Principles of Interaction between Muscle and Bone > 2.1. Physical Forces
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In the paper
“In bone, the primary cilium appears to be an important mediator of gravity and consecutive osteogenic response, because in simulated microgravity, the cilium gradually shrinks and inhibition of this shrinkage using cytochalasin D maintains osteoblast differentiation capacity (reviewed in [40]).”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 2. Principles of Interaction between Muscle and Bone > 2.1. Physical Forces
What the sources say
- Not checked yetcites [40] Shi, 2019, Novel functions of the primary cilium in bone disease and cancer, Cytoskelet. source
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In the paper
“IGF-1 and also FGF2 are growth factors that are actively secreted at the muscle and bone interface and if delivered into the circulation may have distant effects on bone formation and remodeling.”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 2. Principles of Interaction between Muscle and Bone > 2.2. Systemic Mutual Interactions of Skeletal Muscle and Bone
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In the paper
“EVs may transport myokines/osteokines, miRNA, and organelles and are involved in the regeneration of both bone and muscle tissue after exercise and injury [70,71,72,73,74].”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 2. Principles of Interaction between Muscle and Bone > 2.2. Systemic Mutual Interactions of Skeletal Muscle and Bone
What the sources say
- Not checked yetcites [70] Bittel, 2019, Contribution of Extracellular Vesicles in Rebuilding Injured Muscles, Front. Physiol. source
- Not checked yetcites [71] Lauritzen, 2013, Contraction and AICAR Stimulate IL-6 Vesicle Depletion From Skeletal Muscle Fibers In Vivo, Diabetes source
- Not checked yetcites [72] Morrell, 2018, Mechanically induced Ca2+ oscillations in osteocytes release extracellular vesicles and enhance bone formation, Bone Res. source
- Not checked yetcites [73] Murray, 2018, Concise Review: Intercellular Communication Via Organelle Transfer in the Biology and Therapeutic Applications of Stem Cells, STEM CELLS source
- Not checked yetcites [74] Trovato, 2019, Extracellular Vesicles: Delivery Vehicles of Myokines, Front. Physiol. source
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In the paper
“Muscle cells, very much like bone, do not express the molecular components of the regulated secretory pathway (RSP), and the vesicle release upon exercise may be the relevant mechanism to deliver IL-6 into the circulation.”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 2. Principles of Interaction between Muscle and Bone > 2.2. Systemic Mutual Interactions of Skeletal Muscle and Bone
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In the paper
“Exercise was reported to downregulate both SOST and DKK-1 serum levels, which marks an important link between muscle and bone via physical impact [78,79].”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 2. Principles of Interaction between Muscle and Bone > 2.2. Systemic Mutual Interactions of Skeletal Muscle and Bone
What the sources say
- Not checked yetcites [78] Davoodi, 2019, Improved carotid intima-media thickness-induced high-intensity interval training associated with decreased serum levels of Dkk-1 and sclerostin in type 2 diabetes, J. Diabetes its Complicat.
- Not checked yetcites [79] Picke, 2018, Differential effects of high-fat diet and exercise training on bone and energy metabolism, Bone source
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In the paper
“One example is the immediate rise of muscle insulin-like growth factor 1 (IGF-1) mRNA after an exercise bout and the significant rise of peripheral blood IGF-1 protein levels after 24 h (not yet significant after 2 h) post exercise, which was gone after 48 h [75].”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 2. Principles of Interaction between Muscle and Bone > 2.2. Systemic Mutual Interactions of Skeletal Muscle and Bone
What the sources say
- Not checked yetcites [75] Annibalini, 2019, Muscle and Systemic Molecular Responses to a Single Flywheel Based Iso-Inertial Training Session in Resistance-Trained Men, Front. Physiol. source
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In the paper
“Small vesicles in muscle, which contain immunoreactive IL-6 and are depleted during exercise, have indeed been described in mice [71].”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 2. Principles of Interaction between Muscle and Bone > 2.2. Systemic Mutual Interactions of Skeletal Muscle and Bone
What the sources say
- Not checked yetcites [71] Lauritzen, 2013, Contraction and AICAR Stimulate IL-6 Vesicle Depletion From Skeletal Muscle Fibers In Vivo, Diabetes source
boosteddirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Similarly, the Hippo pathway has gained attention as an important pathway in mechanotransduction and skeletal physiology. Downstream YAP/TAZ regulation is in fact tightly involved in mechanosensing and mechanotransduction both in bone and muscle as well as in many other cells, especially endothelial cells (see Section 3.3).”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 3. Common Effector Mechanisms in Muscle and Bone from Development to Postnatal Regeneration > 3.2. Common Effectors of Muscle and Bone Interaction Modulate Tissue Formation and Remodeling
What the sources say
- Not checked yetcites [55] Dasgupta, 2019, Control of cellular responses to mechanical cues through YAP/TAZ regulation, J. Boil. Chem. source
- Not checked yetcites [115] Meng, 2018, RAP2 mediates mechanoresponses of the Hippo pathway, Nat. source
- Not checked yetcites [116] Xiang, 2018, The versatile hippo pathway in oral-maxillofacial development and bone remodeling, Dev. Boil. source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“In conclusion, there is convincing evidence that during development, the interaction between physics and biology is boosted by EMT and the acquisition of migratory capacity, and every step of interaction causes and supports biological consequences in terms of lineage commitment and maturation.”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 3. Common Effector Mechanisms in Muscle and Bone from Development to Postnatal Regeneration > 3.1. Role of Common Musculoskeletal Precursor’s Mechanotransduction during Development
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In the paper
“Irisin, a cleaved product of fibronectin type III domain containing (FNDC5) with stimulating effects on bone formation, is also delivered from muscle into the circulation after exercise but may have a dual mode of delivery, shedding of preformed polypeptides and de novo synthesis [81].”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 2. Principles of Interaction between Muscle and Bone > 2.2. Systemic Mutual Interactions of Skeletal Muscle and Bone
What the sources say
- Not checked yetcites [81] Li, 2019, Muscle-bone crosstalk and potential therapies for sarco-osteoporosis, J. Cell. Biochem. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Above all, the PTH1R signaling cascade is especially sensitive to mechanical loading. Anabolic PTH1R signals elicited through bone anabolic treatment using intermittent 1-34 PTH (teriparatide) are almost ineffective under conditions of unloading [113].”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 3. Common Effector Mechanisms in Muscle and Bone from Development to Postnatal Regeneration > 3.2. Common Effectors of Muscle and Bone Interaction Modulate Tissue Formation and Remodeling
What the sources say
- Not checked yetcites [113] Tu, 2016, Control of Bone Anabolism in Response to Mechanical Loading and PTH by Distinct Mechanisms Downstream of the PTH Receptor, J. Bone Miner. Res.
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“TSP-4 is expressed in muscle and bone, has different functions compared to TSP-1 (antiangiogenic), and recently has been assigned to angiogenesis and matrix remodeling [94].”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 2. Principles of Interaction between Muscle and Bone > 2.2. Systemic Mutual Interactions of Skeletal Muscle and Bone
What the sources say
- Not checked yetcites [94] Stenina-Adognravi, O., and Plow, E.F. (2019). Thrombospondin-4 in tissue remodeling. Matrix Boil., 300–313. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Joint structures as important features of the musculoskeletal functional unit develop under the influence of respective core signaling cascades of osteogenic, chondrogenic, and ligamentogenic pathways. This process is fundamentally influenced by mechanical forces already in utero, directed by movement of the fetus [45,101].”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 3. Common Effector Mechanisms in Muscle and Bone from Development to Postnatal Regeneration > 3.1. Role of Common Musculoskeletal Precursor’s Mechanotransduction during Development
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“These data demonstrate that there are genes whose expression is relevant for tissue formation in both bone and muscle, and others cause antagonistic effects in the brother tissues.”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 3. Common Effector Mechanisms in Muscle and Bone from Development to Postnatal Regeneration
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In the paper
“Notch signaling has also been reported to be involved in skeletal physiology. We and others recently reported that this pathway is mechanosensitive in skeletal precursors [58,114].”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 3. Common Effector Mechanisms in Muscle and Bone from Development to Postnatal Regeneration > 3.2. Common Effectors of Muscle and Bone Interaction Modulate Tissue Formation and Remodeling
What the sources say
- Not checked yetcites [58] Ziouti, F., Ebert, R., Rummler, M., Krug, M., Müller-Deubert, S., Lüdemann, M., Jakob, F., Willie, B.M., and Jundt, F. (2019). NOTCH Signaling Is Activated through Mechanical Strain in Human Bone Marrow-Derived Mesenchymal Stromal Cells. Stem Cells Int., 2019. source
- Not checked yetcites [114] Canalis, 2018, Notch in skeletal physiology and disease, Osteoporos. Int. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Interestingly, the early genes such as proinflammatory cytokines IL-1b, IL-6, IL-8, the toll-like receptor 4 (TLR4) ligands serum amyloid A1 (SAA1) and SAA2, CYR61/CCN1, connective tissue growth factor (CTGF/CCN2), angiopoietin-like 4 (ANGPTL4) and ANGPTL2 very closely resemble genes that are also relevant in the initial phase of osteogenic differentiation and contribute to angiogenesis in fract”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 2. Principles of Interaction between Muscle and Bone > 2.2. Systemic Mutual Interactions of Skeletal Muscle and Bone
What the sources say
- Not checked yetcites [91] Ebert, 2015, Acute phase serum amyloid A induces proinflammatory cytokines and mineralization via toll-like receptor 4 in mesenchymal stem cells, Stem Cell Res. source
- Not checked yetcites [92] Loi, 2016, Inflammation, fracture and bone repair, Bone source
- Not checked yetcites [93] Sass, F.A., Fuchs, M., Pumberger, M., Geissler, S., Duda, G.N., Perka, C., and Schmidt-Bleek, K. (2018). Immunology Guides Skeletal Muscle Regeneration. Int. J. Mol. Sci., 19. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“The lists of muscle-related transcripts and secreted proteins comprised 149 proteins of unassigned functions as putative interactors with other tissues and 123 transcripts that corresponded to putative myokines including BMPs, chemokines, cytokines, growth/differentiation factors (GDFs), and members of the tumor necrosis factor (TNF) family of secreted proteins and ligands for Wnt signaling (Suppl”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 2. Principles of Interaction between Muscle and Bone > 2.2. Systemic Mutual Interactions of Skeletal Muscle and Bone
What the sources say
- Not checked yetcites [90] Zhang, 2018, Transcriptional profiling reveals extraordinary diversity among skeletal muscle tissues, eLife source
hedged- Asserted: passes — The authors put it forward as true.
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In the paper
“Bone formation and bone resorption are both part of the adaptive refinement and remodeling processes, which are mechanically guided and where both osteoblasts and osteoclasts respond to physical forces [117,118].”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 3. Common Effector Mechanisms in Muscle and Bone from Development to Postnatal Regeneration > 3.2. Common Effectors of Muscle and Bone Interaction Modulate Tissue Formation and Remodeling
What the sources say
- Not checked yetcites [117] Amarasekara, D.S., Yun, H., Kim, S., Lee, N., Kim, H., and Rho, J. (2018). Regulation of Osteoclast Differentiation by Cytokine Networks. Immune Netw., 18. source
- Not checked yetcites [118] Ma, 2019, The role of physical forces in osteoclastogenesis, J. Cell. Physiol. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“However, there are some other populations that substantially contribute to regeneration such as the Sca1+/CD34+ fibro-adipogenic progenitors (FAPs) residing in the muscle interstitium. Following injury, satellite cells re-enter the cell cycle and proliferate to give rise to myoblasts that differentiate and fuse to restore the damaged fiber or generate myofibers de novo, while FAPs support their”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 3. Common Effector Mechanisms in Muscle and Bone from Development to Postnatal Regeneration > 3.2. Common Effectors of Muscle and Bone Interaction Modulate Tissue Formation and Remodeling
What the sources say
- Not checked yetcites [131] Baghdadi, 2018, Regulation and phylogeny of skeletal muscle regeneration, Dev. Boil. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Very much in analogy with bone and probably many other tissues, the initial phase of regeneration is governed by intrinsic inflammatory signals and is further induced by cells of the innate immune system, e.g. sequentially recruited neutrophils and resident macrophages. Cytokines already known from bone regeneration such as IL-1, 6, and 8 are involved in innate immune cell recruitment until the”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 3. Common Effector Mechanisms in Muscle and Bone from Development to Postnatal Regeneration > 3.2. Common Effectors of Muscle and Bone Interaction Modulate Tissue Formation and Remodeling
What the sources say
- Not checked yetcites [132] Dort, J., Fabre, P., Molina, T., and Dumont, N.A. (2019). Macrophages Are Key Regulators of Stem Cells during Skeletal Muscle Regeneration and Diseases. Stem Cells Int., 2019. source
- Not checked yetcites [133] Mukund, 2019, Skeletal muscle: A review of molecular structure and function, in health and disease, Wiley Interdiscip. Rev. Syst. Boil. Med. source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Both Pax7-deficient and satellite cell-deficient mice fail to regenerate muscle [131].”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 3. Common Effector Mechanisms in Muscle and Bone from Development to Postnatal Regeneration > 3.2. Common Effectors of Muscle and Bone Interaction Modulate Tissue Formation and Remodeling
What the sources say
- Not checked yetcites [131] Baghdadi, 2018, Regulation and phylogeny of skeletal muscle regeneration, Dev. Boil. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Not only is this condition in common for regenerating tissues in the early phase, but it also somehow mimics the senescence-associated secretory phenotype (SASP) of presenescent and senescent cells. It appears to be beneficial if intermittent, but it causes pathology if chronically active.”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 3. Common Effector Mechanisms in Muscle and Bone from Development to Postnatal Regeneration > 3.2. Common Effectors of Muscle and Bone Interaction Modulate Tissue Formation and Remodeling
What the sources say
- Not checked yetcites [109] Czarkwiani, 2018, Out with the old, in with the new: senescence in development, Curr. Opin. Cell Boil. source
- Not checked yetcites [125] Farr, 2019, Cellular senescence in bone, Bone source
- Not checked yetcites [126] He, 2017, Senescence in Health and Disease, Cell source
- Not checked yetcites [127] Rhinn, 2019, Cellular senescence in development, regeneration and disease, Dev. source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Satellite stem cell development in addition to Pax3 expression is largely dependent on the expression of Pax7 in the pre- and perinatal periods and modulated by mechanical strain [32].”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 3. Common Effector Mechanisms in Muscle and Bone from Development to Postnatal Regeneration > 3.2. Common Effectors of Muscle and Bone Interaction Modulate Tissue Formation and Remodeling
What the sources say
- Not checked yetcites [32] Jin, 2019, Physicochemical Niche Conditions and Mechanosensing by Osteocytes and Myocytes, Curr. Osteoporos. Rep. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In case of bone, we and others have recently reported that there are no significant associations to epigenetic marks or aging associated DNA signatures in peripheral blood mononuclear cells in age-related osteoporosis, while others claim to see such associations, and the debate is ongoing [159,160,161].”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 3. Common Effector Mechanisms in Muscle and Bone from Development to Postnatal Regeneration > 3.4. Epigenetic Changes Shape Individual Responses According to Lifestyle, Environment, and Aging
What the sources say
- Not checked yetcites [159] Riancho, 2018, Epigenetics of Skeletal Diseases, Curr. Osteoporos. Rep. source
- Not checked yetcites [160] Eipel, 2017, Primary Osteoporosis Is Not Reflected by Disease-Specific DNA Methylation or Accelerated Epigenetic Age in Blood, J. Bone Miner. Res.
- Not checked yetcites [161] Jakob, 2018, Response to Letter to the Editor: Epigenetic Aging in Osteoporosis, J. Bone Miner. Res. source
plain- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In conclusion, there are basically two systems to mutually communicate between muscle and bone where physics and biochemistry meet. Physical forces exerted by physical load, muscle activity (contraction and relaxation), and fluid flow are translated into biochemical signals and the biology of cells and tissues. The primary biological response to physical cues changes the receiving biological”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 3. Common Effector Mechanisms in Muscle and Bone from Development to Postnatal Regeneration > 3.5. Conclusions–Two Systems of Mutual Communication between Muscle and Bone
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“muscle satellite cells attract and cross-talk with EC via vascular endothelial growth factor (VEGF) secretion, while the EC-derived Notch ligand Dll4 causes muscle stem cell quiescence and creates a vascular niche [151].”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 3. Common Effector Mechanisms in Muscle and Bone from Development to Postnatal Regeneration > 3.3. Influence of Tissue Resident Cell Populations on Tissue Regeneration and Mechanoadaptation–A Focus on Immune Cell Interactions and Angiogenesis
What the sources say
- Not checked yetcites [151] Verma, 2018, Muscle Satellite Cell Cross-Talk with a Vascular Niche Maintains Quiescence via VEGF and Notch Signaling, Cell Stem Cell source
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“When focusing on muscle and bone, the most obvious mechanisms that trigger diseases in both compartments are unloading and chronic inflammation, which will be discussed in the following sections for translational perspectives.”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 4. Muscle and Bone Interactions in Disease—Lessons and Backflashes from Pathology
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper may give no reason why it holds.
In the paper
“In addition, evidence showed that macrophage PPARƴ (peroxisome proliferator-activated receptor γ) expression controls the delivery of growth differentiation factor-3 (GDF3) and is almost essential for muscle regeneration [139].”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 3. Common Effector Mechanisms in Muscle and Bone from Development to Postnatal Regeneration > 3.3. Influence of Tissue Resident Cell Populations on Tissue Regeneration and Mechanoadaptation–A Focus on Immune Cell Interactions and Angiogenesis
What the sources say
- Not checked yetcites [139] Varga, 2016, Macrophage PPARγ, a Lipid Activated Transcription Factor Controls the Growth Factor GDF3 and Skeletal Muscle Regeneration, Immun. source
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“For bone, it has been demonstrated that endothelial specification strongly contributes to microarchitectural structures—for example, cortical versus trabecular bone. Moreover, there is again an important contribution of Notch signaling since the process of endothelium specification and its mutual interaction with osteogenesis is Notch dependent [146,147,148,149,150].”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 3. Common Effector Mechanisms in Muscle and Bone from Development to Postnatal Regeneration > 3.3. Influence of Tissue Resident Cell Populations on Tissue Regeneration and Mechanoadaptation–A Focus on Immune Cell Interactions and Angiogenesis
What the sources say
- Not checked yetcites [146] Chen, 2016, Endothelial cells are progenitors of cardiac pericytes and vascular smooth muscle cells, Nat. Commun. source
- Not checked yetcites [147] Chopra, 2018, Insights into Endothelial Progenitor Cells: Origin, Classification, Potentials, and Prospects, Stem Cells Int. source
- Not checked yetcites [148] Kusumbe, 2014, Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone, Nat. source
- Not checked yetcites [149] Ramasamy, 2014, Endothelial Notch activity promotes angiogenesis and osteogenesis in bone, Nat. source
- Not checked yetcites [150] Sivaraj, 2016, Blood vessel formation and function in bone, Dev. source
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“With respect to exercise as a countermeasure of bone and muscle loss, there is evidence that exercise is followed by epigenetic changes that besides modulating the accessibility of chromatin regions for adaptive signaling even determine the availability of metabolic intermediates for acetylation and methylation. Moreover, many of these epigenetic effects remain as signatures that may even have a”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 3. Common Effector Mechanisms in Muscle and Bone from Development to Postnatal Regeneration > 3.4. Epigenetic Changes Shape Individual Responses According to Lifestyle, Environment, and Aging
What the sources say
hedgeddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“EC do strongly respond to mechanical cues, and one important target for their mechanoresponse is again the Notch pathway [152].”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 3. Common Effector Mechanisms in Muscle and Bone from Development to Postnatal Regeneration > 3.3. Influence of Tissue Resident Cell Populations on Tissue Regeneration and Mechanoadaptation–A Focus on Immune Cell Interactions and Angiogenesis
What the sources say
- Not checked yetcites [152] Mack, 2018, NOTCH regulation of the endothelial cell phenotype, Curr. Opin. Hematol. source
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“What appears to be quite obvious is that skeletal precursors obtained from the bone marrow of osteoporotic patients harbor an almost diagnostic signature of their transcriptome, while the putatively epigenetic hubs of regulation await further identification [162].”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 3. Common Effector Mechanisms in Muscle and Bone from Development to Postnatal Regeneration > 3.4. Epigenetic Changes Shape Individual Responses According to Lifestyle, Environment, and Aging
What the sources say
- Not checked yetcites [162] Benisch, P., Schilling, T., Klein-Hitpass, L., Frey, S.P., Seefried, L., Raaijmakers, N., Krug, M., Regensburger, M., Zeck, S., and Schinke, T. (2012). The Transcriptional Profile of Mesenchymal Stem Cell Populations in Primary Osteoporosis Is Distinct and Shows Overexpression of Osteogenic Inhibitors. PLOS ONE, 7. source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“A recently published meta-analysis including 75 µG simulation studies reported moderate changes on muscle parameters within 7–14 days of µG and large effects on muscle force, mass, and peak power after 35 days [166].”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 4. Muscle and Bone Interactions in Disease—Lessons and Backflashes from Pathology > 4.1. Unloading–Lessons from Bed Rest Studies and Microgravity
What the sources say
- Not checked yetcites [166] Winnard, 2019, Effect of Time on Human Muscle Outcomes During Simulated Microgravity Exposure Without Countermeasures—Systematic Review, Front. Physiol. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Overall, tissue regeneration appears to be a teamwork that requires the interactions of several cell populations including tissue-specific precursors, immune cells, and endothelial precursors, whereby also the latter seem to be tissue specific, and this applies to both muscle and bone [153].”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 3. Common Effector Mechanisms in Muscle and Bone from Development to Postnatal Regeneration > 3.3. Influence of Tissue Resident Cell Populations on Tissue Regeneration and Mechanoadaptation–A Focus on Immune Cell Interactions and Angiogenesis
What the sources say
- Not checked yetcites [153] Wosczyna, 2018, A Muscle Stem Cell Support Group: Coordinated Cellular Responses in Muscle Regeneration, Dev. Cell source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Overall, very much in analogy to bone regeneration, also muscle regeneration starts with an inflammatory reaction that activates the myofiber-specific amplification and differentiation process and ends up in tissue remodeling according to mechanical challenge.”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 3. Common Effector Mechanisms in Muscle and Bone from Development to Postnatal Regeneration > 3.2. Common Effectors of Muscle and Bone Interaction Modulate Tissue Formation and Remodeling
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Restorative macrophages even orchestrate the interaction between myogenic cells and endothelial precursors during muscle regeneration. Interestingly, the main signaling molecules involved were apelin (APLN), oncostatin M (OSM), and periostin (POSTN), which are also important for bone regeneration [138].”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 3. Common Effector Mechanisms in Muscle and Bone from Development to Postnatal Regeneration > 3.3. Influence of Tissue Resident Cell Populations on Tissue Regeneration and Mechanoadaptation–A Focus on Immune Cell Interactions and Angiogenesis
What the sources say
- Not checked yetcites [138] Latroche, 2017, Coupling between Myogenesis and Angiogenesis during Skeletal Muscle Regeneration Is Stimulated by Restorative Macrophages, Stem Cell Rep. source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“None of the modalities can actually measure muscle mass, but lean mass and muscle volume are used as surrogates.”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 4. Muscle and Bone Interactions in Disease—Lessons and Backflashes from Pathology > 4.2. Inflammation and Fatty Degeneration—Lessons from Imaging and Structural Analyses
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Bioimpedance analysis systems estimate fat and fat-free mass from the electrical impedance measurements of trunk, arms, and legs using age, gender, and ethnic-specific algorithms validated in previous studies, albeit with large prediction errors for individuals [180].”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 4. Muscle and Bone Interactions in Disease—Lessons and Backflashes from Pathology > 4.2. Inflammation and Fatty Degeneration—Lessons from Imaging and Structural Analyses
What the sources say
- Not checked yetcites [180] Kyle, 2004, Bioelectrical impedance analysis?part I: review of principles and methods, Clin. Nutr. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Inflammation and disuse also propagate muscle fatty infiltration and bone marrow adipose expansion, which even more contributes to inflammatory activity initiating a vicious cycle.”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 4. Muscle and Bone Interactions in Disease—Lessons and Backflashes from Pathology > 4.2. Inflammation and Fatty Degeneration—Lessons from Imaging and Structural Analyses
What the sources say
- Not checked yetcites [91] Ebert, 2015, Acute phase serum amyloid A induces proinflammatory cytokines and mineralization via toll-like receptor 4 in mesenchymal stem cells, Stem Cell Res. source
- Not checked yetcites [107] Gilbert, 2019, The consequences of ageing, progeroid syndromes and cellular senescence on mechanotransduction and the nucleus, Exp. Cell Res. source
- Not checked yetcites [108] Serrano, 2014, Cellular senescence: from physiology to pathology, Nat. Rev. Mol. Cell Boil. source
- Not checked yetcites [109] Czarkwiani, 2018, Out with the old, in with the new: senescence in development, Curr. Opin. Cell Boil. source
- Not checked yetcites [177] Schell, 2011, Inflammatory phase of bone healing initiates the regenerative healing cascade, Cell Tissue Research
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“T1 images are used for the assessment of intermuscular adipose tissue (IMAT), which is the ensemble of ‘white voxels’ within the fascia lata (FL) [181].”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 4. Muscle and Bone Interactions in Disease—Lessons and Backflashes from Pathology > 4.2. Inflammation and Fatty Degeneration—Lessons from Imaging and Structural Analyses
What the sources say
- Not checked yetcites [181] Karampinos, 2011, Characterization of the regional distribution of skeletal muscle adipose tissue in type 2 diabetes using chemical shift-based water/fat separation, J. Magn. Reson. Imaging source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Neither DXA nor BIA can provide three-dimensional (3D) measurements.”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 4. Muscle and Bone Interactions in Disease—Lessons and Backflashes from Pathology > 4.2. Inflammation and Fatty Degeneration—Lessons from Imaging and Structural Analyses
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“As expected, the adenosine monophosphate-activated protein kinase (AMPK) that functions as a main signal transduction mechanism for muscle hypertrophy was identified [173].”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 4. Muscle and Bone Interactions in Disease—Lessons and Backflashes from Pathology > 4.1. Unloading–Lessons from Bed Rest Studies and Microgravity
What the sources say
- Not checked yetcites [173] Vilchinskaya, N.A., Krivoi, I.I., and Shenkman, B.S. (2018). AMP-Activated Protein Kinase as a Key Trigger for the Disuse-Induced Skeletal Muscle Remodeling. Int. J. Mol. Sci., 19. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The quote only partly states this claim.
In the paper
“The former provides a quantitative measurement of lean (but not of muscle) mass and of fat mass of the total body or a sub part of it (Table 2).”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 4. Muscle and Bone Interactions in Disease—Lessons and Backflashes from Pathology > 4.2. Inflammation and Fatty Degeneration—Lessons from Imaging and Structural Analyses
What the sources say
- Not checked yetcites [178] Buckinx, 2018, Pitfalls in the measurement of muscle mass: a need for a reference standard, J. Cachex- Sarcopenia Muscle source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“While inflammation is an essential part of the initial phase of tissue regeneration, the failure of timely resolution through anti-inflammatory cytokines is key for these roadblocks and it also drives aging and the manifestations of an inflammatory senescence-associated phenotype (SASP) [91,107,108,109,177].”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 4. Muscle and Bone Interactions in Disease—Lessons and Backflashes from Pathology > 4.2. Inflammation and Fatty Degeneration—Lessons from Imaging and Structural Analyses
What the sources say
- Not checked yetcites [91] Ebert, 2015, Acute phase serum amyloid A induces proinflammatory cytokines and mineralization via toll-like receptor 4 in mesenchymal stem cells, Stem Cell Res. source
- Not checked yetcites [107] Gilbert, 2019, The consequences of ageing, progeroid syndromes and cellular senescence on mechanotransduction and the nucleus, Exp. Cell Res. source
- Not checked yetcites [108] Serrano, 2014, Cellular senescence: from physiology to pathology, Nat. Rev. Mol. Cell Boil. source
- Not checked yetcites [109] Czarkwiani, 2018, Out with the old, in with the new: senescence in development, Curr. Opin. Cell Boil. source
- Not checked yetcites [177] Schell, 2011, Inflammatory phase of bone healing initiates the regenerative healing cascade, Cell Tissue Research
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In analogy to Dixon imaging, with CT, a muscle density measured in Hounsfield units (HU) (0 HU for water and–1000 HU for air) can be quantified.”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 4. Muscle and Bone Interactions in Disease—Lessons and Backflashes from Pathology > 4.2. Inflammation and Fatty Degeneration—Lessons from Imaging and Structural Analyses
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The value of muscle tissue (about 50–60 HU) is lowered by the infiltration of lipids.”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 4. Muscle and Bone Interactions in Disease—Lessons and Backflashes from Pathology > 4.2. Inflammation and Fatty Degeneration—Lessons from Imaging and Structural Analyses
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In clinical routine, the preferred method is semi-quantitative assessment of muscle and adipose tissue area or volume from T1 weighted MR images, which show very good contrast between these two tissues (see Figure 3 top left and top right showing T1 weighted images from a young healthy normal male and from an elderly male with sarcopenia).”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 4. Muscle and Bone Interactions in Disease—Lessons and Backflashes from Pathology > 4.2. Inflammation and Fatty Degeneration—Lessons from Imaging and Structural Analyses
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“It impairs mechanotransduction and triggers the production of inhibitors of regeneration in both compartments, namely myostatin, activin, SOST, and DKK-1 under various clinical conditions.”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 4. Muscle and Bone Interactions in Disease—Lessons and Backflashes from Pathology > 4.2. Inflammation and Fatty Degeneration—Lessons from Imaging and Structural Analyses
What the sources say
- Not checked yetcites [91] Ebert, 2015, Acute phase serum amyloid A induces proinflammatory cytokines and mineralization via toll-like receptor 4 in mesenchymal stem cells, Stem Cell Res. source
- Not checked yetcites [107] Gilbert, 2019, The consequences of ageing, progeroid syndromes and cellular senescence on mechanotransduction and the nucleus, Exp. Cell Res. source
- Not checked yetcites [108] Serrano, 2014, Cellular senescence: from physiology to pathology, Nat. Rev. Mol. Cell Boil. source
- Not checked yetcites [109] Czarkwiani, 2018, Out with the old, in with the new: senescence in development, Curr. Opin. Cell Boil. source
- Not checked yetcites [177] Schell, 2011, Inflammatory phase of bone healing initiates the regenerative healing cascade, Cell Tissue Research
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Chronic inflammation can be both a cause and consequence of disuse and atrophy in muscle and bone.”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 4. Muscle and Bone Interactions in Disease—Lessons and Backflashes from Pathology > 4.2. Inflammation and Fatty Degeneration—Lessons from Imaging and Structural Analyses
What the sources say
- Not checked yetcites [91] Ebert, 2015, Acute phase serum amyloid A induces proinflammatory cytokines and mineralization via toll-like receptor 4 in mesenchymal stem cells, Stem Cell Res. source
- Not checked yetcites [107] Gilbert, 2019, The consequences of ageing, progeroid syndromes and cellular senescence on mechanotransduction and the nucleus, Exp. Cell Res. source
- Not checked yetcites [108] Serrano, 2014, Cellular senescence: from physiology to pathology, Nat. Rev. Mol. Cell Boil. source
- Not checked yetcites [109] Czarkwiani, 2018, Out with the old, in with the new: senescence in development, Curr. Opin. Cell Boil. source
- Not checked yetcites [177] Schell, 2011, Inflammatory phase of bone healing initiates the regenerative healing cascade, Cell Tissue Research
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Both tissues sense mechanical strain, transduce biochemical signals in response, and mutually influence the respective tissue architecture to balance muscle power and fracture resistance.”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 5. Conclusions and Perspectives
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Epigenetics is strongly involved in aging phenomena, and recent research indicates that both positive exercise and training effects and also exercise resistance and degeneration can be modulated by epigenetic mechanisms.”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 5. Conclusions and Perspectives
boostedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Continuous adaptive remodeling appears to be the key to delay aging-associated degeneration; hence, exercise and locomotion in concerted interaction between muscle and bone are core phenomena of health maintenance in higher organisms.”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 5. Conclusions and Perspectives
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Interestingly, the combination of soft tissue parameters discriminated hip fractures as well as a combination of trabecular BMD and cortical thickness, documenting a strong interaction between muscle and bone structure using fatty infiltration and other soft tissue architectural parameters as surrogate parameters.”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 4. Muscle and Bone Interactions in Disease—Lessons and Backflashes from Pathology > 4.2. Inflammation and Fatty Degeneration—Lessons from Imaging and Structural Analyses
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Physical strain is transformed into a multitude of biochemical signals that causes modeling or remodeling until a new state of homeostasis is reached as long as the physical input remains in a steady state.”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 5. Conclusions and Perspectives
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It is physical strain that strongly modulates the biology of cells along their lineage commitment and maturation as well as the hypertrophy versus atrophy of tissues according to physical challenge.”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 5. Conclusions and Perspectives
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
The paper relies on this without support.
Muscle and bone are derived from common precursors during development.
“Muscle and bone are derived from common precursors during development, indicating a close relationship and interaction.”
The paper relies on this without support.
There are currently no guidelines by which imaging parameter(s) should be quantified to address a given muscle composition question.
“Currently, there are no guidelines by which imaging parameter(s) should be quantified to address a given muscle composition question.”
The paper relies on this without support.
Comparative studies on imaging parameters for muscle composition are still missing.
“Comparative studies are still missing.”
The paper relies on this without support.
A direct comparison of CT muscle density with MRI Dixon FF results has not been published.
“Interestingly, to the best of our knowledge, a direct comparison of CT muscle density with MRI Dixon FF results has not been published so far.”
The paper relies on this without support.
The borders to pathology, which stimulus hurts cells, and which one stimulates adaptive remodeling are not yet exactly known.
“We are beginning to understand the mechanisms of regulation, but we do not yet exactly know where the borders to pathology begin, which stimulus hurts cells, and which one stimulates adaptive remodeling.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“The principal products secreted from bone that influence the formation, maintenance and regeneration of muscle are the osteocalcin, a marker protein of osteoblasts, and FGF23, a phosphatonin derived from osteocytes, as well as the inhibitors of the osteogenic wingless (Wnt) signaling pathway, sclerostin [136].”
From Exerkines and Sarcopenia: Unveiling the Mechanism Behind Exercise-Induced Mitochondrial Homeostasis (2025) · cites this paper as [136]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Interactions between Muscle and Bone—Where Physics Meets Biology > 2. Principles of Interaction between Muscle and Bone > 2.2. Systemic Mutual Interactions of Skeletal Muscle and Bone
“Seminal work on the muscle cell secretory transcriptome and proteome was published in 2012 by Le Bihan et al. and Terry et al [89,90]”
§ Interactions between Muscle and Bone—Where Physics Meets Biology > References
“90. E Terry E. Zhang X. Hoffmann C. Hughes L.D. A Lewis S. Li J. Wallace M.J. A Riley L. Douglas C.M. A Gutierrez-Monreal M. Transcriptional profiling reveals extraordinary diversity among skeletal muscle tissues eLife 2018 7 e34613”
Citations
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MethodCellular senescence: from physiology to pathology
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Metadata
- Authors
- Herrmann, M., Engelke, K., Ebert, R., Müller-Deubert, S., Rudert, M., Ziouti, F., Jundt, F., Felsenberg, D., & Jakob, F.
- Affiliations
- University of Würzburg (DE)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Universitätsklinikum Würzburg (DE)
- Privatpraxis für Muskel- und Knochenkrankheiten, 12163 Berlin Germany
- Corresponding author
- Jakob, Franz
- ORCID
- Venue
- Biomolecules
- Publisher
- MDPI AG
- Published
- 2020-03-10
- Volume
- 10
- Issue
- 3
- Pages
- 432
- ISSN
- 2218-273X (ISSN-L)
- PMC
- PMC7175139
- OpenAlex
- W3010713274
- Cited by
- 197
- References
- 217
- Citations by year
- 2026: 23 · 2025: 41 · 2024: 43 · 2023: 32 · 2022: 33 · 2021: 17 · 2020: 6
- FWCI
- 2.11
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- Biomolecules (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Online Publication Service of Würzburg University (Würzburg University) (submittedVersion, cc-by)
- OPUS Repository (Kooperativer Bibliotheksverbund Berlin-Brandenburg) (submittedVersion, cc-by)
- Funders
- Deutsche Forschungsgemeinschaft (TRR 225, JU426/5-1, 326998133, 01EC1402C, D-361)
- Bundesministerium für Bildung und Forschung (326998133-TRR 225, 01EC1402C, 326998133)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Health Sciences › Medicine › Physiology (medical) › Spaceflight effects on biology
- Keywords
- muscle-bone interaction, mechanotransduction, osteokines, myokines, exosomes, extracellular matrix, muscle hypertrophy, bone formation, physical activity, microgravity, disuse, sarcopenia, osteoporosis, bone marrow adiposity, tissue stiffness
- MeSH terms
- Bone and Bones, Extracellular Matrix, Humans, Osteoporosis, Exercise, Muscle, Skeletal, Mechanotransduction, Cellular, Sarcopenia
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