Dexamethasone Induced Osteocyte Apoptosis in Steroid‐Induced Femoral Head Osteonecrosis through ROS ‐Mediated Oxidative Stress

作者：Xinglong Zhang, Zhenhuan Yang, Qian Xu, Chunlei Xu, Wei Shi, Ran Pang, Kai Zhang, Xinyu Liang, Hui Li, Zhijun Li, Huafeng Zhang · 发表于：Orthopaedic Surgery · 年份：2024 · DOI：10.1111/os.14010 · 被引用次数：21 · 研究领域：Bone and Joint Diseases、Hip disorders and treatments、Orthopaedic implants and arthroplasty

OBJECTIVE: Glucocorticoid (GC) overuse is strongly associated with steroid-induced osteonecrosis of the femoral head (SINFH). However, the underlying mechanism of SINFH remains unclear. This study aims to investigate the effect of dexamethasone (Dex)-induced oxidative stress on osteocyte apoptosis and the underlying mechanisms. METHODS: Ten patients with SINFH and 10 patients with developmental dysplasia of the hips (DDH) were enrolled in our study. Sixty rats were randomly assigned to the Control, Dex, Dex + N-Acetyl-L-cysteine (NAC), Dex + Dibenziodolium chloride (DPI), NAC, and DPI groups. Magnetic resonance imaging (MRI) was used to examine edema in the femoral head of rats. Histopathological staining was performed to assess osteonecrosis. Immunofluorescence staining with TUNEL and 8-OHdG was conducted to evaluate osteocyte apoptosis and oxidative damage. Immunohistochemical staining was carried out to detect the expression of NOX1, NOX2, and NOX4. Viability and apoptosis of MLO-Y4 cells were measured using the CCK-8 assay and TUNEL staining. 8-OHdG staining was conducted to detect oxidative stress. 2',7'-Dichlorodihydrofluorescein diacetate (DCFH-DA) staining was performed to measure reactive oxygen species (ROS). The expression of NOX1, NOX2, and NOX4 in MLO-Y4 cells was analyzed by Western blotting. Multiple comparisons were performed using one-way analysis of variance (ANOVA). RESULTS: In patients and the rat model, hematoxylin-eosin (HE) staining revealed a significa...