{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T15:35:29Z","timestamp":1766158529513,"version":"3.37.3"},"reference-count":55,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2020,8,24]],"date-time":"2020-08-24T00:00:00Z","timestamp":1598227200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["RC2018\/2019 and RC2019\/2020"],"award-info":[{"award-number":["RC2018\/2019 and RC2019\/2020"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The etiology of intervertebral disc degeneration is largely unknown, but local neuroinflammation may exert a crucial role through activation of cells as microglia and pro\u2010inflammatory cytokines production. We aimed to compare the effect of degenerated and normal intervertebral disc microenvironment on microglial cells and the potential role of sphingosine\u20101\u2010phosphate, a pro\u2010inflammatory sphingolipid, in their crosstalk. Human degenerated intervertebral discs (Pfirrmann grade IV) were obtained at surgery for spondylolisthesis. Normal intervertebral discs were collected from cadaveric normal lumbar spines. Normal and degenerated\u2010intervertebral discs were kept in culture to obtain media conditioning. Then, microglial cells were cocultured with conditioned media and viability, proliferation, migration, chemotaxis, and inflammatory gene expression were evaluated. The results demonstrate that conditioned media from degenerated intervertebral discs activate microglial cells, increasing chemotaxis, migration, and pro\u2010inflammatory mediators release to a great extent than normal discs. In addition, we show that the administration of sphingosine\u20101\u2010phosphate to normal intervertebral disc\/microglia coculture mimicked degenerative effects. Interestingly, sphingosine\u20101\u2010phosphate content in conditioned media from degenerated discs was significantly higher than that from normal ones. In addition, FTY720, a functional antagonist of sphingosine\u20101\u2010phosphate, potently inhibited the effect of degenerated intervertebral discs on microglial inflammatory factor transcription and migration. Our data report, for the first time, that sphingosine\u20101\u2010phosphate is involved as signal in the microenvironment of human degenerated intervertebral discs. Sphingosine\u20101\u2010phosphate signaling modulation by FTY720 may induce beneficial effects in counteracting microglial activation during intervertebral disc degeneration.<\/jats:p>","DOI":"10.1002\/jor.24827","type":"journal-article","created":{"date-parts":[[2020,8,12]],"date-time":"2020-08-12T02:36:39Z","timestamp":1597199799000},"page":"1479-1495","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Inflammatory interactions between degenerated intervertebral discs and microglia: Implication of sphingosine\u20101\u2010phosphate signaling"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0097-9146","authenticated-orcid":false,"given":"Stefania E.","family":"Navone","sequence":"first","affiliation":[{"name":"Laboratory of Experimental Neurosurgery and Cell Therapy, Neurosurgery Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico  Milan Italy"},{"name":"\"Aldo Ravelli\" Research Center  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rolando","family":"Campanella","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Neurosurgery and Cell Therapy, Neurosurgery Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Guarnaccia","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Neurosurgery and Cell Therapy, Neurosurgery Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico  Milan Italy"},{"name":"Department of Clinical Sciences and Community Health University of Milan  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean A.","family":"Ouellet","sequence":"additional","affiliation":[{"name":"McGill Scoliosis and Spine Group, Department of Surgery McGill University  Montreal QC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Locatelli","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Neurosurgery and Cell Therapy, Neurosurgery Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico  Milan Italy"},{"name":"\"Aldo Ravelli\" Research Center  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Cordiglieri","sequence":"additional","affiliation":[{"name":"Imaging Facility, National Institute for Molecular Genetics (INGM)  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6465-7624","authenticated-orcid":false,"given":"Roberta","family":"Gualtierotti","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Community Health University of Milan  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Gaudino","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Ciniglio Appiani","sequence":"additional","affiliation":[{"name":"Clinical Pathology Unit, Istituto di Medicina Aerospaziale \"A. 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