Salidroside alleviates dexamethasone‐induced inhibition of bone formation via transforming growth factor‐beta/Smad2/3 signaling pathway

Abstract Glucocorticoid‐induced osteoporosis is the third epidemic osteoporosis following postmenopausal and senileosteoporosis. According to one study, salidroside made ovariectomized rats' bones strong. Salidroside's potential for treating glucocorticoid‐induced osteoporosis remains unproven. This study aimed to investigate the protective effect and mechanism of salidroside on dexamethasone‐induced osteogenic differentiation and bone formation in MC3T3‐E1 cells and zebrafish. The study proved that salindroside had no harmful impact on MC3T3E1 cells. Salidroside significantly relieved dexamethasone‐induced inhibition of ALP (alkaline phosphatase) activity and mineralization in MC3T3‐E1 cells, and promoted osteogenic differentiation of cells. Salidroside increased the expression of osteopontin (OPN), runt‐related transcription factor 2 (Runx2), osterix (Osx), transforming growth factor‐beta (TGF‐β) proteins and promoted the phosphorylation of Smad2/3 in MC3T3‐E1 cells treated with dexamethasone. In addition, the effect of salidroside in relieving dexamethasone‐induced inhibition of osteogenic differentiation in MC3T3‐E1 cells can be blocked by TGF‐β receptor type I/II inhibitor (LY2109761). At the same time, we found that salidroside significantly alleviated the inhibition of dexamethasone‐induced bone formation in zebrafish and promoted the mineralization of zebrafish skulls. LY2109761 reversed the protective impact of salidroside on dexamethasone‐mediated bone impairment in zebrafish. These findings suggested that salidroside alleviated dexamethasone‐induced inhibition of osteogenic differentiation and bone formation via TGF‐β/Smad2/3 signaling pathway.