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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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MSC response to inflammatory factors released from the bone fracture site, such as PDGFs and BMPs, activates BMP-Smad1/5/8 signaling, promoting MSC migration.
“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]
The Results section (“PDGF-AA induces MSC migration via Smad1/5/8”) reports that PDGF-AA induces MSC migration, partly through BMP-Smad1/5/8 signaling; the Discussion links PDGF-AA released at a wound to MSC recruitment during fracture healing. The source does not establish that these factors are released from a fracture site as inflammatory factors, and its Results specify that PDGF-AA, but not PDGF-AB or PDGF-BB, activates Smad1/5/8. Page numbers were not supplied in the passages. (LLM, conf=0.86)
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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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