Astragalus polysaccharide ameliorates steroid-induced osteonecrosis of femoral head through miR-206/HIF-1α/BNIP3 axis

Declining autophagy and rising apoptosis are the main factors driving the development of steroid-induced osteonecrosis of the femoral head (SONFH). Here, we showed that astragalus polysaccharide (APS) improved femoral head necrosis via regulation of cell autophagy and apoptosis through microRNA (miR)-206/hypoxia inducible factor-1 (HIF-1 alpha)/BCL2 interacting protein 3 (BNIP3) axis. The expression of miR-206, HIF-1 alpha, and BNIP3 in SONFH specimens and cell model were measured using qPCR. SONFH cell model was treated with APS. Cell autophagy was evaluated using LC3-immunofluorescence assays. Flow cytometry was conducted to assess cell apoptosis. Apoptosis-related proteins and autophagy-related proteins were determined using western blot. Besides, dual-luciferase reporter assay was employed to investigate the relationship between miR-206 and HIF-1 alpha. Here we showed that miR-206 expression was upregulated in SONFH tissues and cell model. APS promoted autophagy and inhibited apoptosis in SONFH cell model via downregulating miR-206. What is more, HIF-1 alpha was the target of miR-206. Knockdown of HIF-1 alpha reversed the recovery effect of miR-206 inhibitor on SONFH cell model. Furthermore, BNIP3 was the target of HIF-1 alpha. HIF-1 alpha overexpression promoted autophagy and inhibited apoptosis, and knockdown of BNIP3 abolished the recovery effect of HIF-1 alpha overexpression in SONFH cell model. These results provided evidence that APS reduced miR-206 expression, and the downregulated miR-206 increased BNIP3 expression by targeting HIF-1 alpha to promote autophagy and inhibit bone cell apoptosis. Our research proved that APS effectively improved SONFH by regulating cell autophagy and apoptosis.

Automated summary

Declining autophagy and increasing apoptosis are key factors in steroid-induced osteonecrosis of the femoral head (SONFH). Astragalus polysaccharide (APS) was shown to improve the condition by regulating cell autophagy and apoptosis through the miR-206/HIF-1 alpha/BNIP3 axis. The upregulation of miR-206 in SONFH tissues and cell models was responsible for promoting autophagy and inhibiting apoptosis, with APS counteracting this by downregulating miR-206.