The DOI matches its Crossref record; 56 of the 57 references it cites were found in a registry or an index.
PDGF-AA Promotes Osteogenic Differentiation and Migration of Mesenchymal Stem Cell by Down-Regulating PDGFRα and Derepressing BMP-Smad1/5/8 Signaling
Open accessAbstract
Platelet-derived growth factors (PDGFs) play important roles in skeletal development and bone fracture healing, yet how PDGFs execute their functions remains incompletely understood. Here we show that PDGF-AA, but not -AB or -BB, could activate the BMP-Smad1/5/8 pathway in mesenchymal stem cells (MSCs), which requires BMPRIA as well as PDGFRα. PDGF-AA promotes MSC osteogenic differentiation through the BMP-Smad1/5/8-Runx2/Osx axis and MSC migration via the BMP-Smad1/5/8-Twist1/Atf4 axis. Mechanistic studies show that PDGF-AA activates BMP-Smad1/5/8 signaling by feedback down-regulating PDGFRα, which frees BMPRI and allows for BMPRI-BMPRII complex formation to activate smad1/5/8, using BMP molecules in the microenvironment. This study unravels a physical and functional interaction between PDGFRα and BMPRI, which plays an important role in MSC differentiation and migration, and establishes a link between PDGF-AA and BMPs pathways, two essential regulators of embryonic development and tissue homeostasis.
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“This process is triggered by the response of MSCs to inflammatory factors released from the bone fracture site, such as PDGFs and BMPs, which activate BMP-Smad1/5/8 signaling, promoting MSC migration [40,77,78].”
From Mesenchymal Stem/Stromal Cells: Immunomodulatory and Bone Regeneration Potential after Tumor Excision in Osteosarcoma Patients (2023) · cites this paper as [78]
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PERSPECTIVE ARTICLE: Growth factors and cytokines in wound healing
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Massagué, J. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3434 · Cited by 3,239
Role of platelet-derived growth factors in physiology and medicinePreprint
Andræ, J., Gallini, R., & Betsholtz, C. (2008) · Genes & Development · doi:10.1101/gad.1653708 · Cited by 2,534
TGF-β and BMP Signaling in Osteoblast Differentiation and Bone Formation
Chen, G., Deng, C., & Li, Y.-P. (2012) · International Journal of Biological Sciences · doi:10.7150/ijbs.2929 · Cited by 1,756
Mice deficient for PDGF B show renal, cardiovascular, and hematological abnormalities.Preprint
Levéen, P., Pekny, M., Gebré‐Medhin, S., Swolin, B., Larsson, E., & Betsholtz, C. (1994) · Genes & Development · doi:10.1101/gad.8.16.1875 · Cited by 1,130
Dorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism
Yu, P. B., Hong, C. C., Sachidanandan, C., Babitt, J. L., Deng, D. Y., Hoyng, S. A., Lin, H. Y.-F., Bloch, K. D., & Peterson, R. T. (2007) · Nature Chemical Biology · doi:10.1038/nchembio.2007.54 · Cited by 1,059
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Roles of PDGF in animal development
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Integrating Patterning Signals: Wnt/GSK3 Regulates the Duration of the BMP/Smad1 Signal
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Recent advances in BMP receptor signaling
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1 of the 57 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
- J Caverzasio, 2013, Predominant role of PDGF receptor transactivation in Wnt3a-induced osteoblastic cell proliferation, J Bone Miner Res, 28, 260, 10.1002/jbmr.1748 · DOI
- AI Caplan, 2011, PDGF in bone formation and regeneration: new insights into a novel mechanism involving MSCs, J Orthop Res, 29, 1795, 10.1002/jor.21462 · DOI · Paper page
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Items 101–101 of 101
Watanabe, M., Ismael, A. C., Asawa, Y., Inaki, R., Komura, H., Shiraishi, K., Harada, T., Huang, Y.-C., Erika, A. O. K. I., Kumagai, K., et al. (2026) · Oral Science International · doi:10.1002/osi2.70069
Metadata
- Authors
- Li, A., Xia, X., Yeh, J., Kua, H., Liu, H., Mishina, Y., Hao, A., & Li, B.
- Affiliations
- Shandong University (CN)
- Shanghai Jiao Tong University (CN)
- University of Michigan (US)
- Corresponding author
- Hao, Aijun
- Li, Baojie
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2014-12-03
- Volume
- 9
- Issue
- 12
- Pages
- e113785
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4254917
- OpenAlex
- W2011964589
- Cited by
- 100
- References
- 57
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 6 · 2023: 14 · 2022: 9 · 2021: 6 · 2020: 16 · 2019: 16 · 2018: 8 · 2017: 9 · 2016: 6 · 2015: 4
- FWCI
- 2.60
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- National Natural Science Foundation of China (81121001, 31071229, 81130039)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Keywords
- PDGF-AA, platelet-derived growth factor, mesenchymal stem cells, osteogenic differentiation, cell migration, PDGFRA, BMP signaling, Smad1/5/8, BMPR-IA, BMPR2, TWIST1, ATF4, feedback regulation, skeletal development, fracture healing
- MeSH terms
- Animals, Cell Differentiation, Cell Movement, Cells, Cultured, Mice, Inbred C57BL, Osteogenesis, Platelet-Derived Growth Factor, Protein Binding, Blotting, Western, Signal Transduction, Down-Regulation, Mice, Knockout, Receptor, Platelet-Derived Growth Factor alpha, RNA Interference, Smad Proteins, Smad1 Protein, Smad5 Protein, Smad8 Protein, Bone Morphogenetic Protein Receptors, Type I, Bone Morphogenetic Protein 2, Mesenchymal Stem Cells
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