| First Author | Li A | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 12 | Pages | e113785 |
| PubMed ID | 25470749 | Mgi Jnum | J:225689 |
| Mgi Id | MGI:5694027 | Doi | 10.1371/journal.pone.0113785 |
| Citation | Li A, et al. (2014) PDGF-AA promotes osteogenic differentiation and migration of mesenchymal stem cell by down-regulating PDGFRalpha and derepressing BMP-Smad1/5/8 signaling. PLoS One 9(12):e113785 |
| abstractText | 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 PDGFRalpha. 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 PDGFRalpha, 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 PDGFRalpha 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. |
