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  3. A new mechanism in steroid-induced osteonecrosis of the femoral head and the protective role of simvastatin

A new mechanism in steroid-induced osteonecrosis of the femoral head and the protective role of simvastatin

  • Exp Cell Res. 2025 Mar 1;446(1):114471. doi: 10.1016/j.yexcr.2025.114471.
Xu-Huan Li 1,  Shi-da Qian 2,  Dan Chen 3,  Zhou-Zhou Li 4,  Kai-Yun Chen 1,  Yong-Ping Pan 1,  Xiu-Hua Lv 5,  Run-Qing Jia 6,  Xue-Feng Yu 7
Affiliations

Affiliations

  • 1 Affiliated Rehabilitation Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
  • 2 Affiliated Rehabilitation Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China; Institute of Orthopaedics, Huizhou Central People's Hospital, Huizhou, Guangdong, China.
  • 3 First Affiliated Hospital of Hengyang Medical School, University of South China, Hengyang, Hunan, China.
  • 4 Affiliated Rehabilitation Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China; Rehabilitation College of Nanchang University, Nanchang, Jiangxi, China.
  • 5 Institute of Orthopaedics, Huizhou Central People's Hospital, Huizhou, Guangdong, China.
  • 6 Department of Biology, Faculty of Environment and Life, Beijing University of Technology, Beijing, China. Electronic address: runqngjia@bjut.edu.cn.
  • 7 Affiliated Rehabilitation Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China. Electronic address: ndsfy00107@ncu.edu.cn.
PMID: 39978720 DOI: 10.1016/j.yexcr.2025.114471
Abstract

Objective: 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).

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords

Apoptosis; Cardiolipin; Femoral head necrosis; Glucocorticoid; Simvastatin.

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