Curcumin preserves bone health compromised by diabetes by inhibiting osteoporosis through regulation of the SIRT3/FoxO3a signalling pathway

Diabetic osteoporosis (DO) is a metabolic bone disorder associated with diabetes mellitus. It is characterized by reduced bone mass, alterations in bone tissue structure as observed under microscopy, increased susceptibility to fractures, and represents one of the complex manifestations of diabetes mellitus in the skeletal system. Hence, it is necessary to prevent and treat DO by enhancing research on its pathogenesis and thereby improving the existing treatment approaches. To explore the mechanism by which curcumin regulates mitochondrial oxidative stress in osteoblasts for treatment of DO via Sirt3/FoxO3a pathway. Firstly, a high-glucose culture model of mouse osteoblast (MC3T3-E1) was established. On this basis, Western Blot and SiRNA techniques were employed to explore the effects of curcumin on the related proteins of SIRT3/FoxO3a, antioxidant enzymes, and mitochondrial function within cells, as well as the osteogenic differentiation of osteoblasts. Eventually, a rat model of diabetic osteoporosis was constructed, and the role of curcumin in regulating the SIRT3/FoxO3a signal to scavenge oxidative stress and restore bone structural integrity in vivo was investigated. The high glucose microenvironment significantly inhibited the cell viability of MC3T3-E1 cells, decreased the level of intracellular antioxidant enzymes, and altered the mitochondrial membrane potential and structure. Curcumin can reverse the mitochondrial oxidative stress damage of MC3T3-E1 and enhance the osteogenic differentiation capacity of cells by activating the SIRT3/FoxO3a pathway. The beneficial effects of curcumin were abolished upon SIRT3 silencing, suggesting that SIRT3/FoxO3a is the principal pathway through which curcumin modulates cellular functions. Based on a rat model of DO, curcumin increased the level of SIRT3 and enhanced bone mineral density and trabecular number in a dose-dependent manner. Curcumin reduces mitochondrial oxidative stress damage through activation of the SIRT3/FoxO3a signaling pathway to improve diabetic osteoporosis.