骨髄間葉系幹細胞におけるAMPK介在性オートファジー活性化を介したカテキンの骨形成分化促進

Catechin (CH) exhibits protective effects on bone metabolism, although its underlying mechanism has remained incompletely understood. This study aimed to investigate the osteogenic-promoting effects of CH and the underlying molecular pathways in bone marrow mesenchymal stem cells (BMSCs) and MC-3T3-E1 pre-osteoblasts. CH exhibited no significant cytotoxicity across a concentration range of 1-100 μg/mL. At optimal concentrations (10 μg/mL), CH markedly enhanced osteogenic differentiation, as indicated by increased alkaline phosphatase (ALP) activity, mineralization, and upregulation of osteogenic markers (Runx2, Opn, Ocn, and Sp7) at both gene and protein levels. Mechanistically, CH activated autophagy, evidenced by elevated LC3-II and reduced P62 expression, and engaged the AMPK signaling pathway-key regulators of osteogenesis and cellular energy homeostasis. Pharmacological inhibition of AMPK (with compound C) or autophagy (with 3-MA) partially suppressed CH-induced osteogenic effects, which were significantly rescued by CH co-treatment. Furthermore, under H2O2-induced oxidative stress, CH effectively enhanced cell viability, reduced intracellular reactive oxygen species (ROS), inhibited NRF2 nuclear translocation, and restored osteogenic differentiation capacity. These findings demonstrate that CH promotes osteogenesis primarily through the AMPK-autophagy axis and reverses oxidative stress-induced suppression of osteogenic differentiation via ROS clearance, highlighting its therapeutic potential for bone defect regeneration and other bone disorders.