Oleanolic acid alleviates steroid-induced osteonecrosis of the femoral head in rats by regulating Wnt/beta-catenin signaling pathway / 中国组织工程研究

ABSTRACT

BACKGROUND:Oleanolic acid can promote osteoblast proliferation and inhibit osteoclast proliferation,thereby improving steroid-induced osteonecrosis of the femoral head,but its specific mechanism of action is not yet fully understood. OBJECTIVE:To explore the mechanism by which oleanolic acid alleviates steroid-induced osteonecrosis of the femoral head in rats by regulating the Wnt/β-catenin signaling pathway. METHODS:Forty Sprague-Dawley rats were randomized into control group,model group,oleanolic acid group and oleanolic acid+sFRP1 group.An animal model of steroid-induced osteonecrosis of the femoral head was established by injecting prednisolone acetate in the latter three groups.Rats in the oleanolic acid group were gavaged with 10 mg/kg/d oleanolic acid and intramuscularly injected with the corresponding saline;rats in the oleanolic acid+sFRP1 group were gavaged with 10 mg/kg/d oleanolic acid and intramuscularly injected with 1 mg/kg/d Wnt inhibitor-sFRP1;and rats in the control and model groups were administered by gavage and intramuscularly injected with equal volumes of saline for 6 weeks.The levels of serum calcium,phosphorus,transforming growth factor-β1,and alkaline phosphatase were detected.Micro-CT was applied to detect femoral morphology.The morphology of femoral tissue was detected by hematoxylin-eosin staining.Cell apoptosis was detected by TUNEL.The levels of Bcl-2,Bax,β-catenin,and Wnt proteins were determined by western blot. RESULTS AND CONCLUSION:Compared with the control group,the trabeculae bone and femoral head of the model group were seriously injured,the serum levels of calcium,phosphorus,and transforming growth factor-β1 were significantly decreased,the levels of Bcl-2,Wnt,and β-catenin proteins in bone tissue were significantly reduced,and the serum alkaline phosphatase level,cell apoptosis rate,and Bax protein level were significantly increased(P<0.05).Compared with the model group,the degree of trabecular thinning in the oleanolic acid group was significantly improved,and the degree of femoral head damage was significantly reduced,serum alkaline phosphatase level,cell apoptosis rate,and Bax protein level were significantly reduced,serum levels of calcium,phosphorus,and transforming growth factor-β1,and levels of Bcl-2,Wnt,and β-catenin proteins in bone tissue were significantly increased(P<0.05).Compared with the oleanolic acid group,the oleanolic acid+sFRP1 group showed opposite changes in the above-mentioned indicators(P<0.05).To conclude,oleanolic acid can improve bone metabolism indicators and trabecular structure and attenuate femoral head necrosis in rats with steroid-induced osteonecrosis of the femoral head,which can be achieved by activating the Wnt/β-catenin signaling pathway.