{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T03:13:00Z","timestamp":1783825980492,"version":"3.55.0"},"reference-count":73,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:00:00Z","timestamp":1767916800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:00:00Z","timestamp":1767916800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000142","name":"Arthritis Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000142","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000142","name":"Arthritis Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000142","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JOR Spine"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Intervertebral disc (IVD) degeneration is a major contributor to back pain and disability. The cause of IVD degeneration is multifactorial, with no disease\u2010modifying treatments. Sex steroids, primarily testosterone and its derivatives, are becoming increasingly common in the clinic for the treatment of low back pain and continue to be used as ergogenic aids in sport. While outcomes at the level of pain and athletic performance are promising, little research has investigated the effects of these hormones on the biology of the IVD and how sex hormones may directly influence joint health and homeostasis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Primary bovine nucleus pulposus (NP) and annulus fibrosus (AF) cells were isolated from 18\u2010month\u2010old female bovine caudal IVDs for primary cell culture. These cells were subjected to sex hormone stimulation (5\u03b1\u2010dihydrotestosterone or 17\u03b2\u2010estradiol) at increasing doses (0, 25, 50, 75, 100, 125\u2009nM) with or without a pro\u2010inflammatory stimulus (IL\u20101\u03b2; 10\u2009ng\/mL or TNF\u03b1; 25\u2009ng\/mL) to model healthy and pro\u2010inflammatory environments, respectively. Cells were harvested for analysis of gene expression, cytokine secretion, and to assess NF\u2010\u03baB signaling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In both NP and AF cells (dihydro)testosterone and 17\u03b2\u2010estradiol decreased proinflammatory gene expression and cytokine release. Changes induced by sex hormones were cell\u2010type dependent and specific to the inflammatory stimulus used. NP cells displayed a robust inflammatory response to IL\u20101\u03b2 compared to TNF\u03b1, while AF cells responded to TNF\u03b1 only, but only at the level of gene expression. Attenuation of inflammatory gene expression by sex hormone exposure was not associated with changes in p65 phosphorylation or NF\u2010\u03baB pathway associated gene expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Sex hormones such as dihydrotestosterone and estrogen play an important role mediating inflammatory signaling in cells of the IVD, finding which could lead to novel therapeutics for IVD degeneration.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jsp2.70152","type":"journal-article","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T15:45:42Z","timestamp":1767973542000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Sex Hormones Attenuate Pro\u2010Inflammatory Gene Expression in Nucleus Pulposus and Annulus Fibrosus Cells in a Cell\u2010Type Specific Manner"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2011-389X","authenticated-orcid":false,"given":"Jeffrey L.","family":"Hutchinson","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry The Bone and Joint Institute, the University of Western Ontario  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew E.","family":"Leung","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry The Bone and Joint Institute, the University of Western Ontario  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6503-9107","authenticated-orcid":false,"given":"Cheryle A.","family":"S\u00e9guin","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry The Bone and Joint Institute, the University of Western Ontario  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,9]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007632-199809010-00012"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)60692-4"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61729-2"},{"key":"e_1_2_11_5_1","first-page":"21","article-title":"Lumbar Disc Disorders and Low\u2010Back Pain: Socioeconomic Factors and Consequences","volume":"88","author":"Katz J. 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