{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T06:10:31Z","timestamp":1788502231799,"version":"build-2803163510"},"reference-count":42,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,12,9]],"date-time":"2023-12-09T00:00:00Z","timestamp":1702080000000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01AR069668"],"award-info":[{"award-number":["R01AR069668"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01AR077760"],"award-info":[{"award-number":["R01AR077760"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R21AR080516"],"award-info":[{"award-number":["R21AR080516"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000070","name":"National Institute of Biomedical Imaging and Bioengineering","doi-asserted-by":"publisher","award":["P41EB027062"],"award-info":[{"award-number":["P41EB027062"]}],"id":[{"id":"10.13039\/100000070","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JOR Spine"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Intervertebral disc degeneration (IDD) is a major cause of low back pain (LBP) worldwide. Sexual dimorphism, or sex\u2010based differences, appear to exist in the severity of LBP. However, it is unknown if there are sex\u2010based differences in the inflammatory, biomechanical, biochemical, and histological responses of intervertebral discs (IVDs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Caudal (Coccygeal\/Co) bone\u2010disc\u2010bone motion segments were isolated from multiple spinal levels (Co8 to Co14) of male and female Sprague\u2013Dawley rats. Changes in motion segment biomechanics and extracellular matrix (ECM) biochemistry (glycosaminoglycan [GAG], collagen [COL], water, and DNA content) were evaluated at baseline and in response to chemical insult (lipopolysaccharide [LPS]) or puncture injury ex vivo. We also investigated the contributions of Toll\u2010like receptor (TLR4) signaling on responses to LPS or puncture injury ex vivo, using a small molecule TLR4 inhibitor, TAK\u2010242.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Findings indicate that IVD motion segments from female donors had greater nitric oxide (NO) release in LPS groups compared to male donors. HMGB1 release was increased in punctured discs, but not LPS injured discs, with no sex effect. Although both male and female discs exhibited reductions in dynamic moduli in response to LPS and puncture injuries, dynamic moduli from female donors were higher than male donors across all groups. In uninjured (baseline) samples, a significant sex effect was observed in nucleus pulposus (NP) DNA and water content. Female annulus fibrosus (AF) also had higher DNA, GAG, and COL content (normalized by\u00a0dry weight), but lower water content than male AF. Additional injury\u2010 and sex\u2010dependent effects were observed in AF GAG\/DNA and COL\/DNA content. Finally, TAK\u2010242 improved the dynamic modulus of female but not male punctured discs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings demonstrate that there are differences in rat IVD motion segments based on sex, and that the response to injury in inflammatory, biomechanical, biochemical, and histological outcomes also exhibit sex differences. TLR4 inhibition protected against loss of mechanical integrity of puncture\u2010injured IVD motion segments, with differences responses based on donor sex.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jsp2.1299","type":"journal-article","created":{"date-parts":[[2023,12,9]],"date-time":"2023-12-09T09:53:37Z","timestamp":1702115617000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Sex differences in the biomechanical and biochemical responses of caudal rat intervertebral discs to injury"],"prefix":"10.1002","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6974-1702","authenticated-orcid":false,"given":"Hagar M.","family":"Kenawy","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering Columbia University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda I.","family":"Nu\u00f1ez","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Columbia University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X\u00f3chitl","family":"Morales","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Columbia University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9655-7839","authenticated-orcid":false,"given":"Lauren E.","family":"Lisiewski","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Columbia University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8504-7980","authenticated-orcid":false,"given":"Kevin G.","family":"Burt","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Columbia University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8339-7768","authenticated-orcid":false,"given":"Min Kyu M.","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Columbia University Irving Medical Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Campos","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Columbia University Irving Medical Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Kiridly","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Columbia University Irving Medical Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clark T.","family":"Hung","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Columbia University  New York New York USA"},{"name":"Department of Orthopedic Surgery Columbia University Irving Medical Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0478-6042","authenticated-orcid":false,"given":"Nadeen O.","family":"Chahine","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Columbia University  New York New York USA"},{"name":"Department of Orthopedic Surgery Columbia University Irving Medical Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,12,9]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.21037\/atm.2020.02.175"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0030-5898(20)31652-7"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.14245\/ns.1938296.148"},{"key":"e_1_2_6_5_1","unstructured":"The Institute for Health Metrics and Evaluation.Global Burden of Disease Study 2019 (GBD 2019) Results. 2020.https:\/\/vizhub.healthdata.org\/gbd-results\/"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.60.11.1040"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.phm.0000156970.96219.48"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ocl.2006.08.001"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2008.12.001"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clineuro.2016.04.008"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jot.2015.09.001"},{"issue":"75","key":"e_1_2_6_12_1","first-page":"188","article-title":"Autopsy evaluation of the extent of degeneration of the lumbar intervertebral discs","volume":"13","author":"Lebkowski WJ","year":"2002","journal-title":"Pol Merkur Lekarski"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007632-198802000-00008"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.37857"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007632\u2010200012010\u201000011"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00586\u2010023\u201007542\u20106"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1117\/1.2812631"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-72081-9"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.036012"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2021.06.014"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2023.1117584"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010017\u201008459\u2010z"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2014.209"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00586\u2010014\u20103442\u20104"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar4274"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0099621"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1097\/BRS.0b013e31826b71f4"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010017\u201017472\u20101"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.24154"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27444"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20160118"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10439\u2010008\u20109476\u20101"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2089"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/0009\u20108981(67)90167\u20102"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/jsp2.1150"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1097\/BRS.0000000000003055"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0005\u20102728(99)00020\u20101"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature00858"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10020\u2010018\u20100023\u20108"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1097\/BRS.0b013e3181624504"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2010.07.004"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5920"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.110.068064"}],"container-title":["JOR SPINE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jsp2.1299","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T12:35:31Z","timestamp":1704976531000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jsp2.1299"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12]]},"references-count":42,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,12]]}},"alternative-id":["10.1002\/jsp2.1299"],"URL":"https:\/\/doi.org\/10.1002\/jsp2.1299","archive":["Portico"],"relation":{},"ISSN":["2572-1143","2572-1143"],"issn-type":[{"value":"2572-1143","type":"print"},{"value":"2572-1143","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12]]},"assertion":[{"value":"2023-05-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e1299"}}