{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T19:00:26Z","timestamp":1768071626109,"version":"3.49.0"},"reference-count":49,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2018,9,11]],"date-time":"2018-09-11T00:00:00Z","timestamp":1536624000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Intervertebral discs (<jats:styled-content style=\"fixed-case\">IVD<\/jats:styled-content>) degeneration, which is caused by ageing or mechanical stress, leads to <jats:styled-content style=\"fixed-case\">IVD<\/jats:styled-content> disease, including back pain and sciatica. The cytokine interleukin (<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>)\u201017A is elevated in <jats:styled-content style=\"fixed-case\">NP<\/jats:styled-content> cells during <jats:styled-content style=\"fixed-case\">IVD<\/jats:styled-content> disease. Here we explored the pharmacotherapeutic potential of <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201017A for the treatment of <jats:styled-content style=\"fixed-case\">IVD<\/jats:styled-content> disease using small\u2010molecule inhibitors that block binding of <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201017A to the <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201017A receptor (<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201017<jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>). Treatment of <jats:styled-content style=\"fixed-case\">NP<\/jats:styled-content> cells with <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201017A increased expression of cyclooxygenase\u20102 (<jats:styled-content style=\"fixed-case\">COX<\/jats:styled-content>\u20102), <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106, matrix metalloproteinase (<jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>)\u20103 and <jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>\u201013. These increases were suppressed by an <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201017A\u2010neutralizing antibody, and small molecules that were identified as inhibitors by binding to the <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201017A\u2010binding region of <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201017<jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>. <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201017A signalling also altered sulphated glycosaminoglycan deposition and spheroid colony formation, while treatment with small\u2010molecule inhibitors of <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201017A attenuated this response. Furthermore, mitogen\u2010activated protein kinase pathways were activated by <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201017A stimulation and induced <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106 and <jats:styled-content style=\"fixed-case\">COX<\/jats:styled-content>\u20102 expression, while small\u2010molecule inhibitors of <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201017A suppressed their expression. Taken together, these results show that <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201017A is a valid target for <jats:styled-content style=\"fixed-case\">IVD<\/jats:styled-content> disease therapy and that small\u2010molecule inhibitors that inhibit the <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201017A\u2013<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201017<jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content> interaction may be useful for pharmacotherapy of <jats:styled-content style=\"fixed-case\">IVD<\/jats:styled-content> disease.<\/jats:p>","DOI":"10.1111\/jcmm.13828","type":"journal-article","created":{"date-parts":[[2018,9,12]],"date-time":"2018-09-12T06:04:27Z","timestamp":1536732267000},"page":"5539-5551","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Effects of interleukin\u201017A in nucleus pulposus cells and its small\u2010molecule inhibitors for intervertebral disc disease"],"prefix":"10.1111","volume":"22","author":[{"given":"Kaori","family":"Suyama","sequence":"first","affiliation":[{"name":"Department of Anatomy and Cellular biology Basic Medical Science Tokai University School of Medicine Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4189-9270","authenticated-orcid":false,"given":"Daisuke","family":"Sakai","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Surgical Science Tokai University School of Medicine Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noriaki","family":"Hirayama","sequence":"additional","affiliation":[{"name":"Institute of Advanced Biosciences Tokai University Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshihiko","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of 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