MiR-141 Modulates Bone Marrow Mesenchymal Stem Cells (BMSCs) Osteogenic/Adipogenic Differentiation Under Oxidative Stress

Abstract

BMSCs Osteogenic differentiation is beneficial to the construction of bone tissue engineering. Oxidative stress can affect BMSCs differentiation. MiR-141 regulates BMSCs proliferation. However, MiR-141’s role in BMSCs osteogenic/adipogenic differentiation under oxidative stress is unclear. Mice BMSCs were assigned into control group; oxidative stress group; and si-MiR-141 group followed by detecting miR-141 level. After 14 days of osteogenesis or adipogenesis induction, RUNX2, OPN and FABP4 mRNA level was analyzed together with analysis of ROS and SOD content, ALP activity and TGFβ/smad signaling protein level by Western blot. Under oxidative stress, MiR-141 was significantly upregulated and RUNX2 and OPN level was decreased, along with increased ROS content and FABP4 level, reduced SOD and ALP activity and expression of TGFβ1 and smad2 (P < 0.05). Transfection of MiR-141 siRNA into BMSCs under oxidative stress down-regulated MiR-141, significantly upregulated RUNX2 and OPN, reduced ROS, elevated SOD activity, downregulated FABP4, and increased ALP activity and TGFβ1 and smad2 expression (P < 0.05). In conclusion, MiR-141 expression is increased in BMSCs under oxidative stress. Down-regulating MiR-141 improves the redox imbalance through TGFβ/smad signaling pathway, promotes osteogenic differentiation of BMSCs and inhibits differentiation to adipocytes.