{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:27:26Z","timestamp":1791404846543,"version":"4.3.3"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T00:00:00Z","timestamp":1708473600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Orthopaedic Surgery"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Glucocorticoid (GC) overuse is strongly associated with steroid\u2010induced osteonecrosis of the femoral head (SINFH). However, the underlying mechanism of SINFH remains unclear. This study aims to investigate the effect of dexamethasone (Dex)\u2010induced oxidative stress on osteocyte apoptosis and the underlying mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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\u2009+\u2009N\u2010Acetyl\u2010L\u2010cysteine (NAC), Dex\u2009+\u2009Dibenziodolium 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\u2010OHdG 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\u2010Y4 cells were measured using the CCK\u20108 assay and TUNEL staining. 8\u2010OHdG staining was conducted to detect oxidative stress. 2\u2032,7\u2032\u2010Dichlorodihydrofluorescein diacetate (DCFH\u2010DA) staining was performed to measure reactive oxygen species (ROS). The expression of NOX1, NOX2, and NOX4 in MLO\u2010Y4 cells was analyzed by Western blotting. Multiple comparisons were performed using one\u2010way analysis of variance (ANOVA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In patients and the rat model, hematoxylin\u2013eosin (HE) staining revealed a significantly higher rate of empty lacunae in the SINFH group than in the DDH group. Immunofluorescence staining indicated a significant increase in TUNEL\u2010positive cells and 8\u2010OHdG\u2010positive cells in the SINFH group compared to the DDH group. Immunohistochemical staining demonstrated a significant increase in the expression of NOX1, NOX2, and NOX4 proteins in SINFH patients compared to DDH patients. Moreover, immunohistochemical staining showed a significant increase in the proportion of NOX2\u2010positive cells compared to the Control group in the femoral head of rats. In vitro, Dex significantly inhibited the viability of osteocyte cells and induced apoptosis. After Dex treatment, the intracellular ROS level increased. However, Dex treatment did not alter the expression of NOX proteins in vitro. Additionally, NAC and DPI inhibited the generation of intracellular ROS and partially alleviated osteocyte apoptosis in vivo and in vitro.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study demonstrates that GC promotes apoptosis of osteocyte cells through ROS\u2010induced oxidative stress. Furthermore, we found that the increased expression of NOXs induced by GC serves as an important source of ROS generation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/os.14010","type":"journal-article","created":{"date-parts":[[2024,2,22]],"date-time":"2024-02-22T01:35:13Z","timestamp":1708565713000},"page":"733-744","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Dexamethasone Induced Osteocyte Apoptosis in Steroid\u2010Induced Femoral Head Osteonecrosis through\n                    <scp>ROS<\/scp>\n                    \u2010Mediated Oxidative Stress"],"prefix":"10.1111","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6950-5539","authenticated-orcid":false,"given":"Xinglong","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Orthopaedics General Hospital of Tianjin Medical University  Tianjin China"},{"name":"Department of Orthopaedics Tianjin Nankai Hospital 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