COX-2 promotes the osteogenic potential of BMP9 through TGF-β1/p38 signaling in mesenchymal stem cells
| Autor: | Hong-Hong Luo, Bai-Cheng He, Jia-Hui Zhu, Yuxi Su, Yi-Xuan Deng, Yan Deng, Ling Li, Yuan-Yuan Yang, Pei-Pei Li |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Aging
MAP Kinase Signaling System p38 mitogen-activated protein kinases Receptor Transforming Growth Factor-beta Type I osteogenic differentiation p38 MAPK BMP9 CREB p38 Mitogen-Activated Protein Kinases Cell Line Transforming Growth Factor beta1 Mice Downregulation and upregulation Osteogenesis TGF-β1 Growth Differentiation Factor 2 Animals Gene silencing biology Chemistry Mesenchymal stem cell Mesenchymal Stem Cells Cell Biology COX-2 Cell biology Mrna level Cyclooxygenase 2 Gene Knockdown Techniques Models Animal Bone Morphogenetic Protein 9 biology.protein Female Research Paper Transforming growth factor |
| Zdroj: | Aging (Albany NY) |
| ISSN: | 1945-4589 |
| DOI: | 10.18632/aging.202825 |
| Popis: | This study investigated the effects of transforming growth factor-β1 (TGF-β1) and cyclooxygenase-2 (COX-2) on bone morphogenetic protein 9 (BMP9) in mesenchymal stem cells (MSCs). We found that BMP9 increased mRNA levels of TGF-β1 and COX-2 in C3H10T1/2 cells. BMP9-induced osteogenic markers were enhanced by TGF-β1 and reduced by TGF-βRI-specific inhibitor LY364947. BMP9 increased level of p-Smad2/3, which were either enhanced or reduced by COX-2 and its inhibitor NS398. BMP9-induced osteogenic markers were decreased by NS398 and it was partially reversed by TGF-β1. COX-2 increased BMP9-induced osteogenic marker levels, which almost abolished by LY364947. BMP9-induced bone formation was enhanced by TGF-β1 but reduced by silencing TGF-β1 or COX-2. BMP9's osteogenic ability was inhibited by silencing COX-2 but partially reversed by TGF-β1. TGF-β1 and COX-2 enhanced activation of p38 signaling, which was induced by BMP9 and reduced by LY364947. The ability of TGF-β1 to increase the BMP9-induced osteogenic markers was reduced by p38-specific inhibitor, while BMP9-induced TGF-β1 expression was reduced by NS398, but enhanced by COX-2. Furthermore, CREB interacted with Smad1/5/8 to regulate TGF-β1 expression in MSCs. These findings suggest that COX-2 overexpression leads to increase BMP9's osteogenic ability, resulting from TGF-β1 upregulation which then activates p38 signaling in MSCs. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|