Osteoporosis (OP), a serious complication of type 2 diabetes mellitus (T2DM) clinically referred to as type 2 diabetic osteoporosis (T2DOP), markedly increases the risk of fragility fractures. Emerging evidence suggests that anthocyanins, a class of natural plant pigments, exert protective effects against OP. Although blueberries represent a major source of anthocyanin extraction, the bone-protective effects and underlying mechanisms of blueberry anthocyanin-rich extracts (BAE) have not been systematically elucidated. In vivo, BAE administration attenuated T2DM-induced bone loss, enhanced osteogenic activity, reduced splenic T-helper 17 cell populations, decreased serum levels of proinflammatory cytokines (interleukin-17A IL-17A, interleukin-1β, interleukin-6, transforming growth factor-β), and inhibited skeletal ferroptosis. In vitro, IL-17A exacerbated high-glucose–induced impairments in MC3T3-E1 cells, including reduced cell viability, compromised osteogenic differentiation, increased oxidative stress, and enhanced ferroptosis. Collectively, these findings indicate that BAE alleviates T2DM-induced bone loss by modulating IL-17A–oxidative-stress axis mediated ferroptosis in osteoblasts under hyperglycemic conditions, providing a mechanistic basis for its potential application in managing T2DOP.
Zhang et al. (Wed,) studied this question.