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

Abstract

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-1α)/BCL2 interacting protein 3 (BNIP3) axis. The expression of miR-206, HIF-1α, 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-1α. 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-1α was the target of miR-206. Knockdown of HIF-1α reversed the recovery effect of miR-206 inhibitor on SONFH cell model. Furthermore, BNIP3 was the target of HIF-1α. HIF-1α overexpression promoted autophagy and inhibited apoptosis, and knockdown of BNIP3 abolished the recovery effect of HIF-1α 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-1α to promote autophagy and inhibit bone cell apoptosis. Our research proved that APS effectively improved SONFH by regulating cell autophagy and apoptosis.Abbreviations: APS, astragalus polysaccharide; SONFH, steroid-induced osteonecrosis of the femoral head; HIF-1α, hypoxia inducible factor-1α; BNIP3, Bcl2 interacting protein 3; miRNA, microRNA; UTR, untranslated region; ONFH, osteonecrosis of the femoral head; IF, immunofluorescence; ANOVA, analysis of variance; qRT-PCR, quantitative real-time polymerase chain reaction; SDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel electrophoresis; WB, western blot.

Mechanism of KDM5A‐mediated H3K4me3 modification in the osteogenic differentiation of mesenchymal stem cells in steroid‐induced osteonecrosis of the femoral head

“…Another study has reported the overexpression of miR‐601 in SONFH, which promotes BMSC senescence by targeting SIRT1 35 . Astragalus polysaccharide downregulates miR‐206, leading to increased hypoxia‐inducible factor‐1 and promotion of autophagy in SONFH cells, thereby inhibiting osteocyte apoptosis 36 . Additionally, miR‐26b is upregulated during the osteogenesis of BMSC induced by osteoactivin 37 .…”

“…35 Astragalus polysaccharide downregulates miR-206, leading to increased hypoxia-inducible factor-1 and promotion of autophagy in SONFH cells, thereby inhibiting osteocyte apoptosis. 36 Additionally, miR-26b is upregulated during the osteogenesis of BMSC induced by osteoactivin. 37 Collectively, we speculate that the role of miR-107 in SONFH may be interconnected with these factors.…”

Astragalus polysaccharide ameliorates steroid-induced osteonecrosis of the femoral head by regulating miR-200b-3p-mediated Wnt/β-catenin signaling pathway via inhibiting SP1 expression

“…Additionally, APS inhibited radiation-triggered bystander effects through suppressing apoptosis in Bone Mesenchymal Stem Cells (BMSCs) [ 29 ]. A recent research indicated that APS alleviated SONFH through promoting autophagy and inhibiting bone cell apoptosis via miR-206/HIF-1α/BNIP3 axis [ 9 ]. Our study revealed that APS could induce osteocyte autophagy and reduce osteocyte apoptosis in DEX-treated MLO-Y4 cells, suggesting that APS may alleviate SONFH progression.…”

“…Moreover, APS could inhibit osteoporosis through modulating FoxO3a/Wnt signaling pathway in ovariectomized rats [ 8 ]. Recently, APS was reported to improve SONFH via regulating cell autophagy and apoptosis [ 9 ]. However, the molecular mechanisms for APS in regulating SONFH remain unclear.…”

Pyroptosis -related potential diagnostic biomarkers in steroid-induced osteonecrosis of the femoral head

“…Patients in the early stage of SONFH did not have any clear symptoms, and the symptoms cannot be reversed, and the incidence rate increased year by year [ 29 ]. But some studies have shown that under the action of glucocorticoid, normal connection mechanism, signal transmission, osteocytes, osteoblasts cannot according to the external stimulus orderly repair, reshape the normal structure, the mechanical properties of the femoral head cannot effectively reconstruct, and cannot restore the normal femoral head mechanical support structure, and exhibit local sclerosis cystic changes, and even collapse [ 30 – 34 ]. Therefore, the early and accurate timing of hip-preserving treatment is the key to the success treatment of SONFH [ 25 ].…”