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Cited by 1,756Bone Metabolism and DiseasesTGF-β signaling in diseasesDevelopmental Biology and Gene Regulation

TGF-β and BMP Signaling in Osteoblast Differentiation and Bone Formation

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Chen, Guiqian, Deng, Chuxia, Li, Yi-Ping·2012·International Journal of Biological Sciences
DOI 10.7150/ijbs.2929PMC PMC3269610
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Abstract

Transforming growth factor-beta (TGF-β)/bone morphogenic protein (BMP) signaling is involved in a vast majority of cellular processes and is fundamentally important throughout life. TGF-β/BMPs have widely recognized roles in bone formation during mammalian development and exhibit versatile regulatory functions in the body. Signaling transduction by TGF-β/BMPs is specifically through both canonical Smad-dependent pathways (TGF-β/BMP ligands, receptors and Smads) and non-canonical Smad-independent signaling pathway (e.g. p38 mitogen-activated protein kinase pathway, MAPK). Following TGF-β/BMP induction, both the Smad and p38 MAPK pathways converge at the Runx2 gene to control mesenchymal precursor cell differentiation. The coordinated activity of Runx2 and TGF-β/BMP-activated Smads is critical for formation of the skeleton. Recent advances in molecular and genetic studies using gene targeting in mice enable a better understanding of TGF-β/BMP signaling in bone and in the signaling networks underlying osteoblast differentiation and bone formation. This review summarizes the recent advances in our understanding of TGF-β/BMP signaling in bone from studies of genetic mouse models and human diseases caused by the disruption of TGF-β/BMP signaling. This review also highlights the different modes of cross-talk between TGF-β/BMP signaling and the signaling pathways of MAPK, Wnt, Hedgehog, Notch, and FGF in osteoblast differentiation and bone formation.

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  • Following bone injury, the bone extracellular matrix releases a physiological amount of growth factors that play a vital role in bone repair.

    “Following bone injury, the bone’s extracellular matrix releases a physiological amount of growth factors which play a vital role in bone repair.”

    From Mesenchymal Stem/Stromal Cells: Immunomodulatory and Bone Regeneration Potential after Tumor Excision in Osteosarcoma Patients (2023) · cites this paper as [72]

    The BMP signaling section describes BMPs as important to bone formation and reports their use in repairing bone defects; the clinical applications section discusses BMP treatment of fractures. However, our copy does not say that bone injury causes the extracellular matrix to release a physiological amount of growth factors. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • Major regulators within the bone remodeling cascade are BMPs, VEGF, FGF, PDGF, TGF-β1, and IGF-1.

    “Among these, major regulators within the bone remodeling cascade are bone morphogenetic proteins (BMPs), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), transforming growth factor-β1 (TGF-β1), and insulin-like growth factor 1 (IGF-1) [39,69,70,71,72,73,74,75,76].”

    From Mesenchymal Stem/Stromal Cells: Immunomodulatory and Bone Regeneration Potential after Tumor Excision in Osteosarcoma Patients (2023) · cites this paper as [72]

    The Introduction and the sections on TGF-β signaling and its interplay with other pathways describe roles for BMPs, TGF-β1, FGF and PDGF-AB in bone formation or osteogenic activity (page numbers unavailable). They do not establish the full six-factor list as major regulators of the bone remodeling cascade; searches for VEGF and IGF-1 did not find support for those two factors in our copy. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • BMP-2 and BMP-7 have gained approval for addressing significant bone defects.

    “Particularly, BMP-2 and BMP-7 have gained approval for addressing significant bone defects [39,72].”

    From Mesenchymal Stem/Stromal Cells: Immunomodulatory and Bone Regeneration Potential after Tumor Excision in Osteosarcoma Patients (2023) · cites this paper as [72]

  • VEGF is essential for angiogenesis and osteogenesis during the normal fracture healing process, facilitating the influx of MSCs that differentiate into osteoblasts via their chemotactic effects.

    “VEGF is essential for angiogenesis and osteogenesis during the normal fracture healing process, facilitating the influx of MSCs that differentiate into osteoblasts via their chemotactic effects [39,71,72,83].”

    From Mesenchymal Stem/Stromal Cells: Immunomodulatory and Bone Regeneration Potential after Tumor Excision in Osteosarcoma Patients (2023) · cites this paper as [72]

    The TGF-β signaling section identifies mesenchymal stem/progenitor cells as osteoblast progenitors, but does not connect their recruitment or differentiation to VEGF. Searches for VEGF, angiogenesis during fracture healing, and VEGF-mediated chemotaxis found no passage addressing the attributed mechanism; the paper’s fracture-healing discussion concerns BMP and FGF instead. No page numbers are available in our copy. (LLM, conf=0.75)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Chen, G., Deng, C., & Li, Y.-P.
Affiliations
University of Alabama at Birmingham (US)
ORCID
Chen, Guiqian
Venue
International Journal of Biological Sciences
Publisher
Ivyspring International Publisher
Published
2012
Volume
8
Issue
2
Pages
272-288
ISSN
1449-2288 (ISSN-L)
DOI
10.7150/ijbs.2929
PMC
PMC3269610
OpenAlex
W2172270516
Cited by
1,756
References
2
Citations by year
2026: 95 · 2025: 138 · 2024: 135 · 2023: 148 · 2022: 135 · 2021: 143 · 2020: 146 · 2019: 128 · 2018: 130 · 2017: 135 · 2016: 128 · 2015: 93 · 2014: 98 · 2013: 78 · 2012: 26
FWCI
8.60
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • International Journal of Biological Sciences (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • National Institutes of Health
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR‐055307, R01AR055307, AR-44741, R01AR044741)
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
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
TGF-beta signaling, BMP signaling, osteogenic differentiation, bone formation, p38 MAPK pathway, Runx2, mesenchymal precursor cells, skeletal development, genetic mouse models, signaling crosstalk, Wnt signaling, Hedgehog signaling, Notch signaling, FGF signaling
MeSH terms
Animals, Cell Differentiation, Gene Expression Regulation, Humans, Osteoblasts, Osteogenesis, Signal Transduction, Transforming Growth Factor beta, Bone Morphogenetic Proteins, Mice

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