Transforming Growth Factor-β1 to the Bone

Janssens, Katrien; ten Dijke, Peter; Janssens, Sophie; Van Hul, Wim

doi:10.1210/er.2004-0001

Cited by 714Bone Metabolism and DiseasesTGF-β signaling in diseasesBone health and osteoporosis research

Transforming Growth Factor-β1 to the Bone

Janssens, Katrien, ten Dijke, Peter, Janssens, Sophie, Van Hul, Wim·2005·Endocrine Reviews

DOI 10.1210/er.2004-0001

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Abstract

TGF-β1 is a ubiquitous growth factor that is implicated in the control of proliferation, migration, differentiation, and survival of many different cell types. It influences such diverse processes as embryogenesis, angiogenesis, inflammation, and wound healing. In skeletal tissue, TGF-β1 plays a major role in development and maintenance, affecting both cartilage and bone metabolism, the latter being the subject of this review. Because it affects both cells of the osteoblast and osteoclast lineage, TGF-β1 is one of the most important factors in the bone environment, helping to retain the balance between the dynamic processes of bone resorption and bone formation. Many seemingly contradictory reports have been published on the exact functioning of TGF-β1 in the bone milieu. This review provides an overall picture of the bone-specific actions of TGF-β1 and reconciles experimental discrepancies that have been reported for this multifunctional cytokine.

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Exercise-associated bone-derived factors that affect bone formation include TGFβ1 and sclerostin.
“Noted exercise-associated bone-derived factors affecting bone formation include TGFβ1 (REF.162) and sclerostin163.”
From Exerkines in health, resilience and disease (2022) · cites this paper as [162]

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Differentiation and Cell Surface Expression of Transforming Growth Factor-β Receptors Are Regulated by Interaction with Matrix Collagen in Murine Osteoblastic Cells
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Transcriptional regulation of osteopontin production in rat osteosarcoma cells by type beta transforming growth factor.
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Human Platelet-Derived Transforming Growth Factor-βStimulates Parameters of Bone Growth in Fetal Rat Calvariae*
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Transforming Growth Factor-β Stimulates Bone Matrix Apposition and Bone Cell Replication in Cultured Fetal Rat Calvariae*
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Critical Role of Smads and AP-1 Complex in Transforming Growth Factor-β-dependent Apoptosis
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Type β transforming growth factor (TGFβ) regulation of alkaline phosphatase expression and other phenotype‐related mRNAs in osteoblastic rat osteosarcoma cells
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Recombinant human interferon-gamma inhibits formation of human osteoclast-like cells.
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The Loss of Smad3 Results in a Lower Rate of Bone Formation and Osteopenia Through Dysregulation of Osteoblast Differentiation and Apoptosis
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Transforming growth factor-beta 1, -beta 2, and -beta 3 secreted by a human glioblastoma cell line. Identification of small and different forms of large latent complexes.
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Conditional deletion of the TGF-β type II receptor in Col2a expressing cells results in defects in the axial skeleton without alterations in chondrocyte differentiation or embryonic development of long bones
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TGF-β1 induces bone closure of skull defects: Temporal dynamics of bone formation in defects exposed to rhTGF-β1
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Estrogen prevents bone loss through transforming growth factor β signaling in T cells
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Chemotactic response of osteoblastlike cells to transforming growth factorβ
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Characterization and autoregulation of latent transforming growth factor beta (TGF beta) complexes in osteoblast-like cell lines. Production of a latent complex lacking the latent TGF beta-binding protein.
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Tumor Necrosis Factor-α Inhibits Transforming Growth Factor-β /Smad Signaling in Human Dermal Fibroblasts via AP-1 Activation
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Enhanced expression of TGF-β and c-fos mRNAs in the growth plates of developing human long bones
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Studies of the Mechanism by which Androgens Enhance Mitogenesis and Differentiation in Bone Cells*
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Glucocorticoid regulation of transforming growth factor beta 1 activity and binding in osteoblast-enriched cultures from fetal rat bone.
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Targeted Disruption in Murine Cells Reveals Variable Requirement for Smad4 in Transforming Growth Factor β-related Signaling
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Bone abnormalities in latent TGF-β binding protein (Ltbp)-3–null mice indicate a role for Ltbp-3 in modulating TGF-β bioavailability
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Local injection of TGF-β increases the strength of tibial fractures in the rat
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TGF-β1–induced migration of bone mesenchymal stem cells couples bone resorption with formation
Tang, Y., Wu, X., Lei, W., Pang, L., Wan, C., Shi, Z., Zhao, L., Nagy, T. R., Peng, X., Hu, J., et al. (2009) · Nature Medicine · doi:10.1038/nm.1979 · Cited by 1,165 · see citing works
Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia
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Role of transforming growth factor-β superfamily signaling pathways in human disease
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The Osteosarcoma Microenvironment: A Complex but Targetable Ecosystem
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The roles and regulatory mechanisms of TGF-β and BMP signaling in bone and cartilage development, homeostasis and disease
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Molecular Biology of Bone Metastasis
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Calcium/calmodulin signaling controls osteoblast growth and differentiation
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“TGF-b1 is a growth factor implicated in the control of proliferation, migration, differentiation, and survival of many cells, including osteoblasts [Janssens et al., 2005].”
Background
Transforming growth factor‐β in stem cells and tissue homeostasis
Xu, X., Zheng, L., Yuan, Q., Zhen, G., Crane, J. L., Zhou, X., & Cao, X. (2018) · Bone Research · doi:10.1038/s41413-017-0005-4 · Cited by 414 · see citing works
Dimorphic effects of Notch signaling in bone homeostasis
Engin, F., Yao, Z., Yang, T., Zhou, G. D., Bertin, T., Jiang, M. M., Chen, Y., Wang, L. E., Zheng, H., Sutton, R. E., et al. (2008) · Nature Medicine · doi:10.1038/nm1712 · Cited by 413 · see citing works
“Activating mutations in transforming growth factor-β in humans is associated with increased bone formation and inhibition of bone resorptio”
Background
The dynamic roles of TGF‐β in cancer
Meulmeester, E., & ten Dijke, P. (2010) · The Journal of Pathology · doi:10.1002/path.2785 · Cited by 391 · see citing works
Cytokine expression pattern in compression and tension sides of the periodontal ligament during orthodontic tooth movement in humans
Garlet, T. P., Coelho, U., Silva, J. S., & Garlet, G. P. (2007) · European Journal Of Oral Sciences · doi:10.1111/j.1600-0722.2007.00469.x · Cited by 340 · see citing works
Paracrine Effect of Mesenchymal Stem Cells Derived from Human Adipose Tissue in Bone Regeneration
Linero, I., & Chaparro, O. (2014) · PLoS ONE · doi:10.1371/journal.pone.0107001 · Cited by 323 · see citing works
TGFβ2-Induced Changes in Human Trabecular Meshwork: Implications for Intraocular Pressure
Fleenor, D. L., Shepard, A. R., Hellberg, P. E., Jacobson, N., Pang, I.-H., & Clark, A. F. (2005) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.05-1060 · Cited by 322 · see citing works
Excessive transforming growth factor-β signaling is a common mechanism in osteogenesis imperfecta
Grafe, I., Yang, T., Alexander, S., Homan, E. P., Lietman, C., Jiang, M. M., Bertin, T., Munivez, E. M., Chen, Y., Dawson, B., et al. (2014) · Nature Medicine · doi:10.1038/nm.3544 · Cited by 307 · see citing works
Model structure and control of bone remodeling: A theoretical study
Pivonka, P., Zimak, J., Smith, D. W., Gardiner, B. S., Dunstan, C. R., Sims, N. A., Martin, T. J., & Mundy, G. R. (2008) · Bone · doi:10.1016/j.bone.2008.03.025 · Cited by 299 · see citing works
Local communication on and within bone controls bone remodeling
Henriksen, K., Neutzsky-Wulff, A. V., Bonewald, L. F., & Karsdal, M. A. (2009) · Bone · doi:10.1016/j.bone.2009.03.671 · Cited by 284 · see citing works
TGF-β Family Signaling in Mesenchymal DifferentiationPreprint
Grafe, I., Alexander, S., Peterson, J. R., Snider, T. N., Lévi, B., Lee, B., & Mishina, Y. M. (2017) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a022202 · Cited by 272 · see citing works
Elucidating the Secretion Proteome of Human Embryonic Stem Cell-derived Mesenchymal Stem Cells
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“For example, Jak-STAT signaling is associated with cardioprotection (35), hematopoiesis (36, 37), and skeletal repair and remodeling (38, 39); MAPK signaling plays a crucial role in many aspects of cardiovascular responses (40, 41), skeletal repair and remodeling (39, 42), and hematopoiesis (43); Toll-like receptor si…”
Background
The Role of Inflammatory Cytokines, the RANKL/OPG Axis, and the Immunoskeletal Interface in Physiological Bone Turnover and Osteoporosis
Weitzmann, M. (2013) · Scientifica · doi:10.1155/2013/125705 · Cited by 270 · see citing works
“…[86] and to blunt osteoclastic bone resorption and ameliorate bone loss induced by ovariectomy in mice [90], multiple myeloma induced osteoclast formation and activity in vitro [91], implant particle-induced osteoclastogenesis [92], and in a rheumatoid arthritis animal model in vivo [93].”
Background
Bone metastasis in prostate cancer: emerging therapeutic strategies
Sturge, J., Caley, M. P., & Waxman, J. (2011) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2011.67 · Cited by 256 · see citing works
Camurati-Engelmann disease: review of the clinical, radiological, and molecular data of 24 families and implications for diagnosis and treatment
Janssens, K., Vanhoenacker, F. M. H. M., Bonduelle, M., Verbruggen, L., Maldergem, L. V., Ralston, S. H., Guañabens, N., Migone, N., Wientroub, S., Divizia, M. T., et al. (2005) · Journal of Medical Genetics · doi:10.1136/jmg.2005.033522 · Cited by 241 · see citing works
Self-citation
The Effect of Inflammation on Bone
Epsley, S., Tadros, S., Farid, A., Kargilis, D., Mehta, S., & Rajapakse, C. S. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2020.511799 · Cited by 242 · see citing works
“Thus, the process of resorption and formation is closely coupled to maintain bone homeostasis (Janssens et al., 2005).”
Background
Osteoblasts in osteoporosis: Past, emerging, and future anabolic targets
Marie, P. J., & Kassem, M. (2011) · European Journal of Endocrinology · doi:10.1530/eje-11-0132 · Cited by 234 · see citing works
Effects of growth factors and cytokines on osteoblast differentiation.
Hughes, F., Turner, W., Belibasakis, G., & Martuscelli, G. (2006) · Periodontology 2000 · doi:10.1111/j.1600-0757.2006.00161.x · Cited by 241 · see citing works
Osteoclast Activity and Subtypes as a Function of Physiology and Pathology—Implications for Future Treatments of Osteoporosis
Henriksen, K., Bollerslev, J., Everts, V. E., & Karsdal, M. A. (2011) · Endocrine Reviews · doi:10.1210/er.2010-0006 · Cited by 230 · see citing works
Accelerated orthodontic tooth movement: Molecular mechanisms
Huang, H., Williams, R. C., & Kyrkanides, S. (2014) · American Journal of Orthodontics and Dentofacial Orthopedics · doi:10.1016/j.ajodo.2014.07.007 · Cited by 231 · see citing works
Primary cilium-dependent signaling mechanisms
Pala, R., Alomari, N., & Nauli, S. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18112272 · Cited by 205 · see citing works
“Transforming growth factor beta (TGF-β) plays major roles in bone development and maintenance metabolism by regulating cellular proliferation, differentiation, matrix deposition, and cell migration [96,97].”
Zinc stimulates osteoblastogenesis and suppresses osteoclastogenesis by antagonizing NF-κB activation
Yamaguchi, M., & Weitzmann, M. (2011) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-011-0852-z · Cited by 212 · see citing works
“These include transforming growth factor beta (TGFb), a potent early osteoblast commitment factor [ 10 ] and a potent recruiter of bone marrow stromal cells to sites of bone resorption [11].”
Osteoimmunology and the influence of pro-inflammatory cytokines on osteoclasts
Zupan, J., Jeras, M., & Marc, J. (2013) · Biochemia Medica · doi:10.11613/bm.2013.007 · Cited by 186 · see citing works
A physiologically based mathematical model of integrated calcium homeostasis and bone remodeling
Peterson, M. C., & Riggs, M. M. (2010) · Bone · doi:10.1016/j.bone.2009.08.053 · Cited by 198 · see citing works
Growth factor delivery for oral and periodontal tissue engineering
Kaigler, D., Cirelli, J. A., & Giannobile, W. V. (2006) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.3.5.647 · Cited by 193 · see citing works
Effects of Bone Matrix Proteins on Fracture and Fragility in Osteoporosis
Sroga, G. E., & Vashishth, D. (2012) · Current Osteoporosis Reports · doi:10.1007/s11914-012-0103-6 · Cited by 192 · see citing works
The multiple facets of periostin in bone metabolism
Merle, B., & Garnero, P. (2012) · Osteoporosis International · doi:10.1007/s00198-011-1892-7 · Cited by 190 · see citing works
Microarray gene expression profiling of osteoarthritic bone suggests altered bone remodelling, WNT and transforming growth factor-β/bone morphogenic protein signalling
Hopwood, B., Tsykin, A., Findlay, D. M., & Fazzalari, N. L. (2007) · Arthritis Research & Therapy · doi:10.1186/ar2301 · Cited by 188 · see citing works
Design of 3D printed scaffolds for bone tissue engineering: A review
Kanwar, S., & Vijayavenkataraman, S. (2021) · Bioprinting · doi:10.1016/j.bprint.2021.e00167 · Cited by 180 · see citing works
Pharmacologic Inhibition of the TGF-β Type I Receptor Kinase Has Anabolic and Anti-Catabolic Effects on Bone
Mohammad, K. S., Chen, C. G., Balooch, G., Stebbins, E. G., McKenna, C. R., Davis, H., Niewolna, M., Peng, X., Nguyen, D. H., Ionova-Martin, S. S., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005275 · Cited by 179 · see citing works
Green tea and bone metabolism
Shen, C., Yeh, J. K., Cao, J., & Wang, J.-S. (2009) · Nutrition Research · doi:10.1016/j.nutres.2009.06.008 · Cited by 178 · see citing works
TGF-β coordinately activates TAK1/MEK/AKT/NFkB and SMAD pathways to promote osteoclast survival
Gingery, A., Bradley, E. W., Pederson, L. G., Ruan, M. M., Horwood, N. J., & Oursler, M. J. (2008) · Experimental Cell Research · doi:10.1016/j.yexcr.2008.06.006 · Cited by 175 · see citing works
The activin A‐follistatin system: potent regulator of human extracellular matrix mineralization
Eijken, M., Swagemakers, S. M. A., Koedam, M., Steenbergen, C., Derkx, P., Uitterlinden, A. G., van der Spek, P. J., Visser, J. A., de Jong, F. H., Pols, H. A. P., et al. (2007) · The FASEB Journal · doi:10.1096/fj.07-8080com · Cited by 175 · see citing works
Targeting pro-inflammatory cytokines following joint injury: acute intra-articular inhibition of interleukin-1 following knee injury prevents post-traumatic arthritis
Furman, B. D., Mangiapani, D., Zeitler, E. M., Bailey, K. N., Horne, P. H., Huebner, J. L., Kraus, V. B., Guilak, F., & Olson, S. A. (2014) · Arthritis Research & Therapy · doi:10.1186/ar4591 · Cited by 171 · see citing works
A Brief Review of Bone Cell Function and Importance
Šromová, V., Sobola, D. S., & Kaspar, P. (2023) · Cells · doi:10.3390/cells12212576 · Cited by 171 · see citing works
“They can be categorized into two main types [68]:”
Background
Human Urothelial Cells Isolation, In Vitro Expansion and Characterization for Evaluating Bio-Engineering Potentials
Muniswami, D. M., Devasia, A., Tharion, G., & Kumar, S. (2018) · doi:10.28967/jscrt.2018.01.18001 · Cited by 169 · see citing works
CD105 Protein Depletion Enhances Human Adipose-derived Stromal Cell Osteogenesis through Reduction of Transforming Growth Factor β1 (TGF-β1) Signaling
Lévi, B., Wan, D. C., Glotzbach, J. P., Hyun, J. S., Januszyk, M., Montoro, D. T., Sorkin, M., James, A. W., Nelson, E. R., Li, S., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.256529 · Cited by 169 · see citing works
Pulsed electromagnetic fields enhance BMP‐2 dependent osteoblastic differentiation of human mesenchymal stem cells
Schwartz, Z., Simon, B. J., Duran, M. A., Barabino, G. A., Chaudhri, R. A., & Boyan, B. D. (2008) · Journal of Orthopaedic Research® · doi:10.1002/jor.20591 · Cited by 166 · see citing works
Control of RANKL gene expression
O’Brien, C. A. (2009) · Bone · doi:10.1016/j.bone.2009.08.050 · Cited by 164 · see citing works
Cytokine-Mediated Bone Destruction in Rheumatoid Arthritis
Jung, S., Kim, K.-W., Yang, C.-W., Park, S.-H., & Ju, J. (2014) · Journal of Immunological Research · doi:10.1155/2014/263625 · Cited by 145 · see citing works
Transforming Growth Factor-β and the Immune Response to Malignant Disease
Teicher, B. A. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-1654 · Cited by 159 · see citing works
TGF-β type II receptor phosphorylates PTH receptor to integrate bone remodelling signalling
Qiu, T., Wu, X., Zhang, F., Clemens, T. L., Wan, M., & Cao, X. (2010) · Nature Cell Biology · doi:10.1038/ncb2022 · Cited by 156 · see citing works
“Therefore, direct phosphorylation of the cytoplasmic domain of PTH1R by TβRII integrates PTH signalling for bone remodelling and TGF-β1 signalling for coupling bone resorption and formatio”
Background
Transforming Growth Factor β1 Induces Osteogenic Differentiation of Murine Bone Marrow Stromal Cells
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0163-769X/05/$20.00/0 Endocrine Reviews 26(6):743–774 Printed in U.S.A. Copyright © 2005 by The Endocrine Society doi: 10.1210/er.2004-0001 Transforming Growth Factor-�1 to the Bone
Janssens, K., ten Dijke, P., Janssens, S., & Hul, W. V. (2013)
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Authors: Janssens, K., ten Dijke, P., Janssens, S., & Van Hul, W.
Affiliations: University of Antwerp (BE)
Department of Molecular Cell Biology (P.t.D.), Leids Universitair Medisch Centrum, 2333 AL Leiden, The Netherlands;
University of Lausanne (CH)
Department of Medical Genetics (K.J., W.V.H.), University of Antwerp, 2610 Antwerp, Belgium;
ORCID: Janssens, Katrien
Janssens, Sophie
Venue: Endocrine Reviews
Publisher: The Endocrine Society
Published: 2005-10-01
Volume: 26
Issue: 6
Pages: 743-774
ISSN: 0163-769X (ISSN-L)
1945-7189
DOI: 10.1210/er.2004-0001
OpenAlex: W2144206769
Cited by: 710
References: 408
Citations by year: 2026: 12 · 2025: 26 · 2024: 24 · 2023: 35 · 2022: 30 · 2021: 30 · 2020: 27 · 2019: 22 · 2018: 23 · 2017: 34 · 2016: 37 · 2015: 26 · 2014: 46 · 2013: 57 · 2012: 47
FWCI: 2.60
Type: journal article
Language: en
Open access: closed
Locations: Endocrine Reviews (publishedVersion)
PubMed (publishedVersion)
Ghent University Academic Bibliography (Ghent University) (submittedVersion)
Funders: Fonds Wetenschappelijk Onderzoek
Universiteit Antwerpen
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
Keywords: TGF-β1, bone metabolism, osteoblasts, osteoclasts, bone remodeling, bone resorption, bone formation, cartilage, skeletal development, cytokine signaling
MeSH terms: Animals, Bone and Bones, Bone Development, Bone Resorption, Cells, Cultured, Humans, Osteoblasts, Osteoclasts, Phenotype, Stem Cells, Signal Transduction, Transforming Growth Factor beta, Protein Isoforms, Transforming Growth Factor beta1

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Transforming Growth Factor-β1 to the Bone

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