Regulation of Wnt Signaling Pathway by Costic Acid Derivative, An Efficient Strategy for Treatment of Glucocorticoid‐Induced Osteoporosis in Rat Model

Abstract

AbstractOsteoporosis leads to a decrease in bone mass, loss of mechanical strength, increase in fracture susceptibility and is a serious medical problem worldwide. The present study investigated the effect of costic acid derivative (CA) on dexamethasone (DXM)‐induced osteoporosis in vitro in osteoblasts and in vivo in rat a model. The results demonstrated that DXM‐mediated reduction in osteoblast viability was effectively prevented by CA treatment in dose‐dependent manner. The DXM‐induced loss of osteoblast viability was completely reversed by CA treatment at 4 μM dose. Treatment of the primary osteoblasts with 0. 5 and 4 μM CD for 72 h reversed DXM‐mediated reduction in ALP activity. The CA treatment significantly (P>0.05) reversed DXM‐mediated lowering of osteoclacin, collagen type‐1 and osteonectin mRNA expression. The CA treatment at 1.5, 3 and 6 mg/kg doses significantly (P>0.05) reversed DXM‐mediated decrease in BMD in rat femurs. Treatment of the rats with CA reversed DXM‐mediated changes in osteocalcin and CTX levels in serum samples. Administration of CA to the rats reversed DXM‐mediated decrease in Wnt, β‐catenin expression and increase in SOST and Dickkopf‐1 level. Docking studies showed that CA interacts with mammalian Wnt‐frizzled complex (6AHY) through conventional H‐bonding. Thus, CA inhibits DXM‐induced dysfunction of osteoblast differentiation in vitro and inhibits osteoporosis development in vivo in rat model. Therefore, CA may be developed as a potential therapeutic agent for treatment of bone damage induced by glucocorticoid (GC)‐mediated osteoporosis.