Silent Information Regulating Factor 2 Related Enzyme 1 Regulates the Formation of Osteoblasts and Osteoclasts Through the AKT/β-Catenin Pathway

Abstract

Bone remodeling participates in osteoporosis (OP). Silent information regulating factor 2 related enzyme 1 (sirtuin1, SIRT1) regulates cell survival, differentiation, metabolism and inflammation. However, the regulatory effect of SIRT1 on the formation of osteoblasts and osteoclasts has not been reported. OP and normal rat BMSCs were assigned into control group, OP group, and SIRT1 group (Resveratrol) followed by measuring cell proliferation by MTT assay, ALP activity, expression of SIRT1, RUNX2 and OP by Real time PCR, AKT/β-catenin signaling protein expression by Western blot. Rat BMSCs were cultured and treated with RANKL to induce osteoclast culture in the presence or absence of Resveratrol followed by analysis of cell proliferation and c-Fos and TRAP expression. SIRT1 expression and secretion in BMSCs cells and supernatant of OP group were significantly reduced and cell proliferation was significantly inhibited along with reduced RUNX2 and OP expression, ALP activity as well as decreased AKT/β-catenin phosphorylation compared to control group (P < 0.05); addition of Resveratrol can significantly reverse the above changes (P <0.05). Resveratrol can significantly promote SIRT1 expression, inhibit osteoclast proliferation, and reduce c-Fos and TRAP expression (P < 0.05). SIRT1 expression is reduced in osteoporosis and its upregulation promotes osteogenesis through AKT/β-catenin pathway, inhibits osteoclast formation, and improves osteoporosis.