Salidroside inhibits steroid-induced avascular necrosis of the femoral head via the PI3K/Akt signaling pathway: Invitro and invivo studies.

Abstract

Dexamethasone (Dex) and other glucocorticoids are widely used to treat serious infections and immunological diseases, however they may cause steroid-induced avascular necrosis of the femoral head (SANFH). Salidroside (Sal) has demonstrated an anti-apoptotic effect on neurocytes by activating the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. In the present study, primary osteoblasts were used in vitro and in rats in vivo to determine the anti-apoptotic effect of Sal on SANFH. The result of the present study demonstrated that pretreatment with Sal increased the cell survival rate while decreasing the cell apoptosis and lactate dehydrogenase release rate. Additionally, Sal also caused the reduction of TUNEL positive cells in TUNEL staining assay. Sal decreased the expression of cleaved caspase-3, cleaved caspase-9, apoptosis regulator BAX and cytochrome C, while it increased the expression of B cell lymphoma-2 and phosphorylated-Akt in Dex-induced osteoblasts. In vivo Sal protected against SANFH in rats by decreasing the percentage of empty lacunae. The present study demonstrated that Sal alleviated Dex-induced osteoblast apoptosis by activating the PI3K/Akt signaling pathway and downregulating caspase-3 expression in osteoblasts. Sal also protected against SANFH in a rat model of SANFH by decreasing the percentage of empty lacunae. The inhibition of the mitochondrial apoptosis pathway was also involved. Further research is required to determine the full underlying mechanisms by which Sal has an effect.