{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T12:11:00Z","timestamp":1788869460434,"version":"build-2803163510"},"reference-count":58,"publisher":"Wiley","issue":"42","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Intervertebral disc degeneration (IDD) is a major cause of low back pain, yet the biological effects of commonly used non\u2010steroidal anti\u2010inflammatory drugs (NSAIDs) on disc cells remain poorly understood. Celecoxib is widely prescribed for IDD\u2010related pain, but its direct influence on IDD has not been systematically examined. Here, we identify a concentration\u2010dependent biphasic effect of celecoxib on nucleus pulposus (NP) cells and uncover the mechanism that converts celecoxib from protective to detrimental. Using interleukin\u20101\u03b2\u2010stimulated NP cells and rat IDD models, we show that low\u2010dose celecoxib (\u226420 \u00b5\n                    <jats:sc>m<\/jats:sc>\n                    ) suppresses inflammation and preserves extracellular matrix (ECM). In contrast, high\u2010dose celecoxib (&gt;20 \u00b5\n                    <jats:sc>m<\/jats:sc>\n                    ) activates a previously unrecognized heat shock protein 90 (HSP90)\/RING\u2010box protein 1 (RBX1)\/cuproptosis axis, leading to copper accumulation, mitochondrial stress, and ECM degradation. Mechanistically, elevated celecoxib induces HSP90 upregulation, which stabilizes RBX1 by reducing its K48\u2010linked ubiquitination. Accumulated RBX1 promotes ATPase copper transporting beta (ATP7B) and its regulator copper metabolism domain containing 1 (COMMD1) degradation, thereby triggering cuproptosis. Pharmacologic inhibition of HSP90 or cuproptosis effectively reverses the detrimental effects of high\u2010dose celecoxib in vivo. Together, these findings define a strict therapeutic window for celecoxib in IDD and reveal a novel HSP90\/RBX1\u2010mediated cuproptosis pathway that mediates its dual effects.\n                  <\/jats:p>","DOI":"10.1002\/advs.75527","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T11:34:08Z","timestamp":1777894448000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Drug\u2010Induced Cuproptosis Defines the Therapeutic Window of Celecoxib in Intervertebral Disc Degeneration via the HSP90\u2010RBX1 Axis"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8666-1974","authenticated-orcid":false,"given":"Youfeng","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Spine Surgery School of Medicine Shanghai East Hospital Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongju","family":"Xiao","sequence":"additional","affiliation":[{"name":"Anhui Medical University  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenghao","family":"Ba","sequence":"additional","affiliation":[{"name":"Anhui Medical University  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Life Sciences The Chinese University of Hong Kong  Shatin, N.T. Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bijun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics School of Medicine Yangpu Hospital Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery School of Medicine Shanghai East Hospital Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufeng","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery School of Medicine Shanghai East Hospital Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haihong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Orthopedics School of Medicine Yangpu Hospital Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhefan Stephen","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Life Sciences The Chinese University of Hong Kong  Shatin, N.T. Hong Kong SAR China"},{"name":"Gerald Choa Neuroscience Institute The Chinese University of Hong Kong  Shatin, N.T. Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Hematology Jiangsu Province Hospital The First Affiliated Hospital of Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1772-8853","authenticated-orcid":false,"given":"Zhaoyu","family":"Ba","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery School of Medicine Shanghai East Hospital Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Desheng","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery School of Medicine Shanghai East Hospital Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,4]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.23736\/S0375\u20109393.24.17843\u20101"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ken396"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.116593"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2024.1492870"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033\u2010025\u201010538\u20108"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1563635"},{"issue":"1","key":"e_1_2_11_8_1","article-title":"Role of Neurogenic Inflammation in Intervertebral Disc Degeneration","volume":"16","author":"Peng B. 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