类固醇(糖皮质激素)诱导的股骨头坏死(SONFH)代表了一种普遍的,进步,和具有挑战性的骨生成和血管生成减少的骨和关节疾病。Omaveloxolone(OMA),一种半合成的含抗氧化剂的油酸三萜类化合物,抗炎,和成骨特性,作为SONFH的潜在治疗剂出现。这项研究调查了OMA对SONFH的治疗影响,并阐明了其潜在的机制。采用地塞米松(DEX)诱导人骨髓间充质干细胞(hBMSCs)和人脐静脉内皮细胞(HUVECs),模拟SONFH细胞的体外环境。各种化验,包括CCK-8,茜素红染色,蛋白质印迹,qPCR,免疫荧光,流式细胞术,还有隧道,用于评估细胞活力,STING/NF-κB信号通路相关蛋白,hBMSCs成骨,HUVEC迁移,血管生成,和凋亡。结果表明,OMA促进DEX诱导的成骨,HUVEC迁移,血管生成,通过抑制STING/NF-κB信号通路抑制hBMSCs凋亡。该实验证据强调了OMA在调节DEX诱导的骨生成中的潜力,HUVEC迁移,血管生成,通过STING/NF-κB通路抑制人骨髓间充质干细胞凋亡,从而为改善SONFH的进展提供了有希望的途径。
Steroid (glucocorticoid)-induced necrosis of the femoral head (SONFH) represents a prevalent, progressive, and challenging bone and joint disease characterized by diminished osteogenesis and angiogenesis. Omaveloxolone (OMA), a semi-synthetic oleanocarpane triterpenoid with antioxidant, anti-inflammatory, and osteogenic properties, emerges as a potential therapeutic agent for SONFH. This study investigates the therapeutic impact of OMA on SONFH and elucidates its underlying mechanism. The in vitro environment of SONFH cells was simulated by inducing human bone marrow mesenchymal stem cells (
hBMSCs) and human umbilical vein endothelial cells (HUVECs) using dexamethasone (DEX).Various assays, including CCK-8, alizarin red staining, Western blot, qPCR, immunofluorescence, flow cytometry, and TUNNEL, were employed to assess cell viability, STING/NF-κB signaling pathway-related proteins,
hBMSCs osteogenesis, HUVECs migration, angiogenesis, and apoptosis. The results demonstrate that OMA promotes DEX-induced osteogenesis, HUVECs migration, angiogenesis, and anti-apoptosis in
hBMSCs by inhibiting the STING/NF-κB signaling pathway. This experimental evidence underscores the potential of OMA in regulating DEX-induced osteogenesis, HUVECs migration, angiogenesis, and anti-apoptosis in
hBMSCs through the STING/NF-κB pathway, thereby offering a promising avenue for improving the progression of SONFH.