Journal
KAOHSIUNG JOURNAL OF MEDICAL SCIENCES
Volume 37, Issue 12, Pages 1089-1100Publisher
WILEY
DOI: 10.1002/kjm2.12426
Keywords
astragalus polysaccharide; BNIP3; HIF-1 alpha; miR-206; steroid-induced osteonecrosis of the femoral head
Categories
Funding
- Chinese Medicine Research Project in Hunan Province [201978]
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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.
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.
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