{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T16:23:37Z","timestamp":1785860617737,"version":"3.56.0"},"reference-count":34,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,9,24]],"date-time":"2021-09-24T00:00:00Z","timestamp":1632441600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81501915"],"award-info":[{"award-number":["81501915"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Orthopaedic Surgery"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate the effect and mechanism of Glucocorticoids (GCs) induced oxidative stress and apoptosis on necrosis of the femoral head in patients and rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Eight patients with steroid\u2010induced avascular necrosis of the femoral head (SINFH) and eight patients with developmental dysplasia of the hips (DDH) were enrolled in our study. In animal model, twenty male Sprague\u2010Dawley rats were randomly divided into two groups (SINFH group and NS group). The SINFH model group received the methylprednisolone (MPS) injection, while control group was injected with normal saline (NS). MRI was used to confirm SINFH rat model was established successfully. Then, the rats were sacrificed 4 weeks later and femoral head samples were harvested. Histopathological staining was preformed to evaluate osteonecrosis. TUNEL staining was performed with 8\u2010OHdG and DAPI immunofluorescence staining to evaluate oxidative injury and osteocyte apoptosis. Immunohistochemistry staining was used to detect Nox1, Nox2, and Nox4 protein expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>MRI showed signs of typical osteonecrosis of femoral head in SIHFH patients. Histopathological staining showed that the rate of empty lacunae in SINFH patients was significantly higher (56.88%\u2009\u00b1\u20099.72% <jats:italic>vs<\/jats:italic> 19.92%\u2009\u00b1\u20094.18%, T\u00a0=\u00a0\u221211.04, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001) than that in DDH patients. The immunofluorescence staining indicated that the TUNEL\u2010positive cell and 8\u2010OHdG\u2010positve cell in SINFH patients were significantly higher (49.32%\u2009\u00b1\u200912.95% <jats:italic>vs<\/jats:italic> 8.00%\u2009\u00b1\u20092.11%, T\u00a0=\u00a0\u22127.04, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.002, 54.6%\u2009\u00b1\u200923.8% <jats:italic>vs<\/jats:italic> 9.75%\u2009\u00b1\u20093.31%, T\u00a0=\u00a0\u22124.17, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.003) compared to the DDH patients. The immunohistochemistry staining showed that the protein expression of NOX1, NOX2 and NOX4 in SINFH patients were significantly increased (64.50%\u2009\u00b1\u20097.57% <jats:italic>vs<\/jats:italic> 37.58%\u2009\u00b1\u20099.23%, T\u00a0=\u00a0\u22123.88, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.018, 90.84%\u2009\u00b1\u20092.93% <jats:italic>vs<\/jats:italic> 49.56%\u2009\u00b1\u200916.47%, T\u00a0=\u00a0\u22125.46, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.001, 85.46%\u2009\u00b1\u20099.3% <jats:italic>vs<\/jats:italic> 40.69%\u2009\u00b1\u20096.77%, T\u00a0=\u00a0\u22128.03, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.001) compared to the DDH patients. In animal model, MRI showed signs of edema of femoral head in MPS group, which represents SINFH rat model was established successfully. Histological evaluation showed the rate of empty lacunae in MPS group was significantly higher (25.85%\u2009\u00b1\u20094.68% <jats:italic>vs<\/jats:italic> 9.35%\u2009\u00b1\u20091.99%, T\u00a0=\u00a0\u22127.96, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001) than that in NS group. The immunofluorescence staining indicated that the TUNEL\u2010positive cell and 8\u2010OHdG\u2010positve cell (in MPS group were significantly increased (31.93%\u2009\u00b1\u20091.01% <jats:italic>vs<\/jats:italic> 11.73%\u2009\u00b1\u20091.16%, T\u00a0=\u00a0\u221232.26, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001, 47.59%\u2009\u00b1\u20091.39% <jats:italic>vs<\/jats:italic> 22.07%\u2009\u00b1\u20092.45%, T\u00a0=\u00a0\u221222.18, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001) compared to the NS group. The immunohistochemistry staining showed that the expression of NOX2 in MPS group was significantly increased (76.77%\u2009\u00b1\u20098.34% <jats:italic>vs<\/jats:italic> 50.32%\u2009\u00b1\u200910.84%, T\u00a0=\u00a0\u22124.74, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.001) compare with NS group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings indicated that GC\u2010induced NOXs expression may be an important source of oxidative stress, which could lead to osteocyte apoptosis in the process of SINFH<\/jats:p><\/jats:sec>","DOI":"10.1111\/os.13127","type":"journal-article","created":{"date-parts":[[2021,9,25]],"date-time":"2021-09-25T01:08:53Z","timestamp":1632532133000},"page":"2145-2152","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Oxidative Stress Induced Osteocyte Apoptosis in Steroid\u2010Induced Femoral Head Necrosis"],"prefix":"10.1111","volume":"13","author":[{"given":"Zhen\u2010Qi","family":"Fan","sequence":"first","affiliation":[{"name":"The Department of Orthopedics Tianjin Medical University General Hospital  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu\u2010Cai","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Tianjin Hospital  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Xu","sequence":"additional","affiliation":[{"name":"Tianjin University of Traditional Chinese Medicine  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi\u2010Jun","family":"Li","sequence":"additional","affiliation":[{"name":"The Department of Orthopedics Tianjin Medical University General Hospital  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010Hao","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, The Shenzhen Second People's Hospital, Health Science Center The First Affiliated Hospital of Shenzhen University  Shenzhen China"},{"name":"Department of pharmacology Kyoto Prefectural University of Medicine  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Li","sequence":"additional","affiliation":[{"name":"The Department of Orthopedics Tianjin Medical University General Hospital  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao\u2010Hui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Tianjin Hospital  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua\u2010Feng","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Department of Orthopedics 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