Salidroside inhibits steroid-induced avascular necrosis of the femoral head via the PI3K/Akt signaling pathway: In�vitro and in�vivo 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.

Induction of PI3K/Akt-Mediated Apoptosis in Osteoclasts Is a Key Approach for Buxue Tongluo Pills to Treat Osteonecrosis of the Femoral Head

“…Nevertheless, only the phosphorylation of PI3K and Akt mainly participate in these physiological activities. Besides, growing numbers of studies have found that cell apoptosis is closely related to the PI3K/Akt pathway ( Xue and Feng, 2018 ; Zhan and Yan, 2020 ). Therefore, we evaluated the effect of BTP on the PI3K/Akt pathway in osteoclasts.…”

Total flavonoids of Rhizoma drynariae ameliorate steroid‑induced avascular necrosis of the femoral head via the PI3K/AKT pathway

“…Previous studies have shown that Dex can induce osteoblast apoptosis and SANFH in rat or human specimens by upregulating caspase-3 ( 20 , 41 ). Bcl-2 is an anti-apoptotic gene, whereas Bax is a pro-apoptotic gene ( 3 ) and studies have reported that the cause of Dex-induced osteoblast apoptosis is the imbalance between Bcl-2 and Bax (mitochondrial dysfunction) ( 42 , 43 ). Additionally, Dex treatment can increase ROS production and excessive ROS may cause cell apoptosis through the mitochondrial-mediated caspase apoptosis pathway ( 44 ).…”

“…Osteonecrosis of the femoral head (ONFH) is one of the most common diseases affecting the hip joint, resulting in severe pain or joint disability ( 1 , 2 ). Steroid-induced avascular necrosis of the femoral head (SANFH) is the most common type of ONFH ( 3 ). If patients with SANFH are not treated properly, the femoral head may collapse, resulting in hip function damage and disability ( 4 , 5 ).…”

Identification of differentially expressed genes in hip cartilage with femoral head necrosis, based on genome‑wide expression profiles

“…The PI3K/Akt pathway is associated with various fundamental cellular processes, including survival, proliferation, growth and differentiation (33). Xue et al (34) reported that Salidroside alleviated the dexamethasone-induced apoptosis of osteoblasts by downregulating caspase-3 and activating the PI3K/Akt signaling pathway in osteoblasts. In addition, the osteogenic differentiation-inducing and bone regenerative properties of graphene-incorporated poly(lactic-co-glycolic acid) were mediated via the activation of the PI3K/Akt/glycogen synthase kinase 3β/β-catenin signaling pathway (35).…”