Department of the Orthopedics of Traditional Chinese Medicine, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China; College of Pharmacy, Chonnam National University, Gwangju, Republic of Korea; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.
School of the 1st Clinical Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
Toxicol Appl Pharmacol. 2023 Sep 15;475:116649. doi: 10.1016/j.taap.2023.116649. Epub 2023 Aug 1.
Steroid-induced avascular necrosis of femoral head (SANFH) is a common disorder worldwide with high disability. Overdose of glucocorticoid (GC) is the most common non-traumatic cause of SANFH. Up until now, there are limited therapeutic strategies for curing SANFH, and the mechanisms underlying SANFH progression remain unclear. Nevertheless, Osteogenic dysfunction is considered to be one of the crucial pathobiological mechanisms in the development of SANFH, which involves mouse bone marrow mesenchymal stem cells (BMSCs) apoptosis and osteogenic differentiation disorder. Ursolic acid (UA), an important component of the Chinese medicine formula Yougui Yin, has a wide range of pharmacological properties such as anti-tumor, anti-inflammatory and bone remodeling. Due to the positive effect of Yougui Yin on bone remodeling, the purpose of this study was to investigate the effects of UA on dexamethasone (DEX)-induced SANFH in vitro and vivo. In vitro, we demonstrated that UA can promote mouse BMSCs proliferation and resist DEX-induced apoptosis by CCK8, Western blotting, TUNEL and so on. In addition, vitro experiments such as ALP and Alizarin red staining assay showed that UA had a beneficial effect on the osteogenic differentiation of mouse BMSCs. In vivo, the results of H&E staining, immunohistochemistry staining, Elisa and micro-CT analysis showed that UA had a bone repair-promoting effect in SANFH model. Moreover, the results of Western blot and TUNEL experiments showed that UA could delay the disease progression of SANFH in mice by inhibiting apoptosis. Overall, our study suggests that UA is a potential compound for the treatment of SANFH.
激素诱导性股骨头坏死（SANFH）是一种全球范围内常见的高致残性疾病。糖皮质激素（GC）过量是导致 SANFH 的最常见非创伤性原因。迄今为止，治疗 SANFH 的方法有限，SANFH 进展的机制仍不清楚。然而，成骨功能障碍被认为是 SANFH 发展的关键病理生物学机制之一，涉及小鼠骨髓间充质干细胞（BMSCs）凋亡和成骨分化障碍。熊果酸（UA）是中药方剂右归丸的重要组成部分，具有广泛的药理作用，如抗肿瘤、抗炎和骨重塑。由于右归丸对骨重塑有积极作用，本研究旨在探讨 UA 对体外和体内地塞米松（DEX）诱导的 SANFH 的影响。在体外，我们通过 CCK8、Western blot、TUNEL 等实验证明，UA 可以促进小鼠 BMSCs 的增殖并抵抗 DEX 诱导的凋亡。此外，ALP 和茜素红染色等体外实验表明，UA 对小鼠 BMSCs 的成骨分化有有益的影响。在体内，H&E 染色、免疫组织化学染色、Elisa 和 micro-CT 分析的结果表明，UA 对 SANFH 模型具有促进骨修复的作用。此外，Western blot 和 TUNEL 实验的结果表明，UA 可以通过抑制细胞凋亡来延缓 SANFH 疾病在小鼠中的进展。总的来说，我们的研究表明 UA 是一种治疗 SANFH 的潜在化合物。
