Li Xu-Huan, Qian Shi-da, Chen Dan, Li Zhou-Zhou, Chen Kai-Yun, Pan Yong-Ping, Lv Xiu-Hua, Jia Run-Qing, Yu Xue-Feng
Affiliated Rehabilitation Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
Affiliated Rehabilitation Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China; Institute of Orthopaedics, Huizhou Central People's Hospital, Huizhou, Guangdong, China.
Exp Cell Res. 2025 Mar 1;446(1):114471. doi: 10.1016/j.yexcr.2025.114471. Epub 2025 Feb 18.
Steroid-induced osteonecrosis of the femoral head (SONFH) is a debilitating bone condition associated with femoral head collapse and hip joint dysfunction. The pathogenesis of SONFH is still not fully elucidated. This study aims to explore the role of mitochondrial cardiolipin metabolism disruption in SONFH and the potential protective effects of simvastatin (SIM).
Osteoblasts were cultured in vitro under high concentrations of dexamethasone (DEX) to mimic the effects of glucocorticoid exposure seen in SONFH. Mitochondrial structural changes and cardiolipin distribution were examined using transmission electron microscopy and confocal microscopy. Osteoblast proliferation and apoptosis were assessed using CCK-8 assays and flow cytometry. Mitochondrial cardiolipin content was quantified by ELISA, while cytochrome c (Cyt-c) expression was measured through Western blotting. Mitochondrial staining with NAO was analyzed using confocal microscopy and flow cytometry.
DEX exposure led to mitochondrial cardiolipin metabolism disorder and redistribution, resulting in significant mitochondrial structural damage. This disruption was associated with increased release of Cyt-c into the cytoplasm, which correlated with heightened osteoblast apoptosis. SIM treatment mitigated these effects, reducing osteoblast apoptosis by preserving mitochondrial function and modulating cardiolipin content and distribution.
This study demonstrates, for the first time, that glucocorticoid-induced disruptions in mitochondrial cardiolipin metabolism contribute to the pathogenesis of SONFH by inducing Cyt-c release and subsequent osteoblast apoptosis. SIM exerts a protective effect by preserving mitochondrial integrity and function, offering a potential therapeutic avenue for treating hormone-induced osteoblast damage in SONFH.
糖皮质激素诱导的股骨头坏死（SONFH）是一种使人衰弱的骨骼疾病，与股骨头塌陷和髋关节功能障碍相关。SONFH的发病机制仍未完全阐明。本研究旨在探讨线粒体心磷脂代谢紊乱在SONFH中的作用以及辛伐他汀（SIM）的潜在保护作用。
在体外高浓度地塞米松（DEX）条件下培养成骨细胞，以模拟SONFH中糖皮质激素暴露的影响。使用透射电子显微镜和共聚焦显微镜检查线粒体结构变化和心磷脂分布。使用CCK-8法和流式细胞术评估成骨细胞增殖和凋亡。通过酶联免疫吸附测定法定量线粒体心磷脂含量，同时通过蛋白质免疫印迹法测量细胞色素c（Cyt-c）表达。使用共聚焦显微镜和流式细胞术分析用NAO进行的线粒体染色。
DEX暴露导致线粒体心磷脂代谢紊乱和重新分布，导致明显的线粒体结构损伤。这种破坏与Cyt-c释放到细胞质中增加有关，这与成骨细胞凋亡增加相关。SIM治疗减轻了这些影响，通过保留线粒体功能和调节心磷脂含量及分布来减少成骨细胞凋亡。
本研究首次证明，糖皮质激素诱导的线粒体心磷脂代谢紊乱通过诱导Cyt-c释放和随后的成骨细胞凋亡，促成了SONFH的发病机制。SIM通过保留线粒体完整性和功能发挥保护作用，为治疗SONFH中激素诱导的成骨细胞损伤提供了一条潜在的治疗途径。
