The intervention of OPG/RANKL/RANK signaling pathway by QGYKL mediated complement C3 and succinylation process on osteoporosis

Abstract

Abstract Introduction: Qiangguyin Keli(QGYKL)is a traditional Chinese medicine formula used in the clinical treatment of osteoporosis for over 20 years. The specific protective mechanism of QGYKL against osteoporosis is still unclear. Previous studies have found that silencing complement C3 can improve osteoporosis. Objective This study aims to investigate the effect of QGYKL on complement C3-related osteoporosis and explore its potential mechanisms. Results Researchers performed bilateral oophorectomy or sham surgery on female mice as a control, and then orally administered QGYKL (20 ml/kg/day) for 8 consecutive weeks, And found that oral administration of QGYKL can reduce complement C3, affect the succinylation key protein SIRT5, and improve osteoporosis; In cell experiments, researchers found that C3 levels increase when osteoclasts or osteoblasts differentiate. Among them, the C3 content changes more significantly during the differentiation process of osteoclasts. Inhibiting the expression of the C3 gene can upregulate the expression of OPG in BM-MSC cells, promote the expression of succinylation key protein SIRT5, and reduce the expression of RANKL. Conclusion These results indicate that QGYKL may improve osteoporosis by affecting the content of complement C3 and the succinylation process of complement C3, and subsequently intervening in the expression of OPG and RANKL.