Objective: Chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) plays an important role in osteoarthritis (OA) treatment. Studies have reported the association of transforming growth factor beta-3 (TGF-β3) with chondrogenic differentiation of BMSCs. In this study, the upstream mechanism and functions of TGF-β3 in chondrogenic differentiation of BMSCs were explored.
Methods and results: Flow cytometry was performed for the positive and negative MSC markers. Chondrogenic differentiation of BMSCs was evaluated by Alcian blue staining. Gene expression and protein expression levels were measured by RT-qPCR and western blotting, respectively. Relationship between let-7a-3p and TGF-β3 was confirmed using bioinformatics analysis, luciferase reporter and RNA pulldown assays. Subcellular distributions of TGF-β3 and let-7a-3p were determined by FISH. In this study, BMSCs were identified to possess the characteristics of mesenchymal stem cells. TGF-β3 was found to induce chondrogenic differentiation of BMSCs. Mechanically, TGF-β3 was verified to be targeted by let-7a-3p. In rescue assays, let-7a-3p overexpression reversed the effects of TGF-β3 overexpression on chondrogenic differentiation of BMSCs.
Conclusion: Let-7a-3p inhibits chondrogenic differentiation of bone marrow mesenchymal stem cells by targeting TGF-β3.
Keywords: BMSCs; Chondrogenic differentiation; TGF-β3; let-7a-3p.
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