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Cited by 1,165Bone Metabolism and DiseasesTGF-β signaling in diseasesBone health and osteoporosis research

TGF-β1–induced migration of bone mesenchymal stem cells couples bone resorption with formation

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Tang, Yi, Wu, Xiangwei, Lei, Weiqi, Pang, Lijuan, Wan, Chao, Shi, Zhenqi, Zhao, Ling, Nagy, Timothy R +6 more·2009·Nature Medicine
DOI 10.1038/nm.1979PMC PMC2727637
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Abstract

Bone remodeling depends on the precise coordination of bone resorption and subsequent bone formation. Disturbances of this process are associated with skeletal diseases, such as Camurati-Engelmann disease (CED). We show using in vitro and in vivo models that active TGF-beta1 released during bone resorption coordinates bone formation by inducing migration of bone marrow stromal cells, also known as bone mesenchymal stem cells, to the bone resorptive sites and that this process is mediated through a SMAD signaling pathway. Analyzing mice carrying a CED-derived mutant TGFB1 (encoding TGF-beta1), which show the typical progressive diaphyseal dysplasia seen in the human disease, we found high levels of active TGF-beta1 in the bone marrow. Treatment with a TGF-beta type I receptor inhibitor partially rescued the uncoupled bone remodeling and prevented the fractures. Thus, as TGF-beta1 functions to couple bone resorption and formation, modulation of TGF-beta1 activity could be an effective treatment for bone remodeling diseases.

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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 [75]

    The Introduction (page unavailable) says factors are released from the bone matrix during osteoclastic resorption, and identifies TGF-β1 as a factor involved in recruiting cells to bone-forming surfaces. It does not establish that bone injury triggers this release, that a physiological amount is released, or that the finding concerns repair after injury rather than bone remodeling. (LLM, conf=0.85)

    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 [75]

    The Results section identifies BMPs, PDGF, IGF-I and TGF-βs as factors found in bone matrix, and identifies TGF-β1 as a primary inducer of stem-cell migration in its assay (page not available). It does not identify VEGF or FGF as major regulators, so it supports only part of the cited list. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • TGF-β1 acts as a chemotactic agent, homing local MSCs for osteogenic differentiation through the SMAD signaling pathway.

    “Simultaneously, TGF-β1 acts as a chemotactic agent, homing local MSCs for osteogenic differentiation through the SMAD signaling pathway [39,75].”

    From Mesenchymal Stem/Stromal Cells: Immunomodulatory and Bone Regeneration Potential after Tumor Excision in Osteosarcoma Patients (2023) · cites this paper as [75]

  • Active TGF-β1 induces osteoblast precursor migration to the site of resorption without affecting differentiation of cells.

    “First, active TGF-β1 induces osteoblast precursor migration to the site of resorption203 without affecting the differentiation of cells.204”

    From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [203]

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Authors
Tang, Y., Wu, X., Lei, W., Pang, L., Wan, C., Shi, Z., Zhao, L., Nagy, T. R., Peng, X., Hu, J., Feng, X., Van Hul, W., Wan, M., & Cao, X.
Affiliations
  • University of Alabama at Birmingham (US)
  • Shihezi University (CN)
  • Tongji Hospital (CN)
Corresponding author
Cao, Xu
ORCID
Venue
Nature Medicine
Publisher
Springer Science and Business Media LLC
Published
2009-07
Volume
15
Issue
7
Pages
757-765
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
DOI
10.1038/nm.1979
PMC
PMC2727637
OpenAlex
W1757602702
Cited by
1,165
References
2
Citations by year
2026: 54 · 2025: 50 · 2024: 55 · 2023: 74 · 2022: 81 · 2021: 85 · 2020: 88 · 2019: 72 · 2018: 92 · 2017: 80 · 2016: 58 · 2015: 81 · 2014: 53 · 2013: 79 · 2012: 65
FWCI
21.85
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • University of Alabama at Birmingham
  • National Institutes of Health
  • State Key Laboratory of Synthetical Automation for Process Industries
  • National Institute of Diabetes and Digestive and Kidney Diseases (Z01DK057501, DK057501, R01DK057501)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR 053973, R01AR053973)
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 mesenchymal stem cells, bone remodeling, bone resorption, bone formation, osteoclasts, osteoprogenitor cells, Smad signaling, Camurati-Engelmann disease, mesenchymal stem cells, cell migration
MeSH terms
Receptor, Transforming Growth Factor-beta Type I, Animals, Bone Marrow Cells, Bone Resorption, Cell Movement, Camurati-Engelmann Syndrome, DNA-Binding Proteins, Humans, Mice, Inbred C57BL, Osteogenesis, Signal Transduction, Bone Remodeling, Protein Serine-Threonine Kinases, Receptors, Transforming Growth Factor beta, Mice, Smad Proteins, Transforming Growth Factor beta1, Mesenchymal Stem Cells

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