Capsaicin-Activated Autophagy Protects BMSCs Function under Oxidative Stress: Mechanisms and Therapeutic Implications

Bone marrow stromal cells (BMSCs) play an important role in bone regeneration, but their functional activity is affected by oxidative stress, which is a key pathological feature of osteoporosis. The aim of this study was to investigate the effects of capsaicin on the proliferation and differentiation of BMSCs under oxidative stress. We assessed cell viability and osteogenic potential of capsaicin on promoting BMSCs survival and enhancing osteogenic capacity under oxidative stress by Cell Counting Kit-8 (CCK-8), reactive oxygen species (ROS) fluorescence staining, alkaline phosphatase (ALP) staining, Alizarin Red S (ARS) staining, Western blot (WB) and Real-time PCR (RT-PCR). Our results indicate that capsaicin improves cell viability, antioxidant capacity, and osteogenic differentiation in rat BMSCs treated with hydrogen peroxide (H2O2). In addition, immunohistochemistry (IHC) analysis revealed that the surface of BMSCs expressed capsaicin receptor transient receptor potential vanilloid protein 1 (TRPV1). More importantly, capsaicin increased Ca2+ influx and autophagy, inhibited phosphorylation of PI3K/AKT/mTOR signaling pathway. In conclusion, capsaicin protects BMSCs function during oxidative stress possibly through inducing TRPV1-mediated Ca2+ influx and mPI3K/AKT/mTOR-activated autophagy. The results suggest the potential of capsaicin as a therapeutic agent for osteoporosis.