{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T13:04:04Z","timestamp":1793279044693,"version":"4.5.0"},"reference-count":42,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2020,9,23]],"date-time":"2020-09-23T00:00:00Z","timestamp":1600819200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Multiple human and animal studies suggest that the upregulation of inflammatory cytokines and other pain\u2010related molecules in degenerated or injured intervertebral discs (IVDs) may cause discogenic low back pain (LBP). We previously reported that macrophages in injured IVD in mice produced inflammatory cytokines, but not other pain\u2010related molecules. CD14 is a monocyte marker expressed mainly by macrophages. The aim of the current study was to evaluate the role of CD14\u2010positive cells in inflammatory cytokine and pain\u2010related molecule expression in human degenerated IVD. IVD samples were harvested from 14 patients, including 10 with lumbar spinal stenosis, four with adult spinal deformity, and one with lumbar disc herniation during spinal interbody fusion surgery. Harvested IVD\u2010derived mononuclear cells were obtained and CD14\u2010positive (+) and CD14\u2010negative (\u2212) cells were separated using CD14 antibody and streptavidin\u2010labeled magnetic beads. Inflammatory cytokines messenger RNA (mRNA) in the CD14(+) and CD14(\u2212) cells, including tumor necrosis factor \u0251 (<jats:italic>TNFA<\/jats:italic>), in, terleukin\u20101\u03b2 (<jats:italic>IL1B<\/jats:italic>) and <jats:italic>IL6<\/jats:italic>, were determined using quantitative polymerase chain reaction (qPCR) and their expression levels were compared. To evaluate factors controlling the regulation of pain\u2010related molecules mRNA expression, cultured CD14(\u2212) and CD14(+) cells from IVDs were stimulated with recombinant human TNF\u2010\u0251 and IL\u20101\u03b2 and levels of pain\u2010related molecules, including calcitonin gene\u2010related peptide (<jats:italic>CGRP<\/jats:italic>) and nerve growth factor (<jats:italic>NGF<\/jats:italic>) were determined using qPCR. Levels of <jats:italic>TNFA, IL1B, IL6<\/jats:italic>, and <jats:italic>NGF<\/jats:italic> in CD14(+) cells were significantly increased compared with those in CD14(\u2212) cells (<jats:italic>TNFA<\/jats:italic>, p\u2009=\u20090.006; <jats:italic>IL1B, p<\/jats:italic>\u2009=\u2009.017; <jats:italic>IL6, p<\/jats:italic>\u2009=\u2009.010; <jats:italic>NGF, p<\/jats:italic>\u2009=\u2009.027). Following <jats:italic>TNFA<\/jats:italic> stimulation, <jats:italic>NGF<\/jats:italic> levels were significantly increased in CD14(\u2212) and CD14(+) cells (CD14(\u2212), <jats:italic>p<\/jats:italic>\u2009=\u2009.003; CD14(+), <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001) and CGRP was significantly increased in CD14(\u2212) IVD cells (<jats:italic>p<\/jats:italic>\u2009=\u2009.040). Following <jats:italic>IL1B<\/jats:italic> stimulation, <jats:italic>NGF<\/jats:italic> levels were significantly increased in CD14(\u2212) cells (<jats:italic>p<\/jats:italic>\u2009=\u2009.004). CD14(+) cells had higher <jats:italic>TNFA, IL1B, IL6<\/jats:italic>, and <jats:italic>NGF<\/jats:italic> expressions than CD14(\u2212) cells in human degenerated IVDs. Additionally, <jats:italic>TNFA<\/jats:italic> stimulation promoted the upregulation of <jats:italic>NGF<\/jats:italic> and <jats:italic>CGRP<\/jats:italic> in CD14(\u2212) cells. These findings suggested that CD14(+) cells directly and indirectly contributed to inflammatory cytokine and pain\u2010related molecule expression in human degenerated IVD. CD14(+) cells might be important in the pathological mechanism of chronic discogenic LBP in humans.<\/jats:p>","DOI":"10.1002\/jor.24839","type":"journal-article","created":{"date-parts":[[2020,8,28]],"date-time":"2020-08-28T19:41:51Z","timestamp":1598643711000},"page":"1755-1762","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Role of CD14\u2010positive cells in inflammatory cytokine and pain\u2010related molecule expression in human degenerated intervertebral discs"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3082-9739","authenticated-orcid":false,"given":"Masayuki","family":"Miyagi","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery Kitasato University School of Medicine  Sagamihara City Kanagawa 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Sciences Research Institute  Chigasaki City Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyuki","family":"Nakazawa","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Kitasato University School of Medicine  Sagamihara City Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Imura","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Kitasato University School of Medicine  Sagamihara City Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wataru","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Kitasato University School of Medicine  Sagamihara City Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiki","family":"Shirasawa","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Kitasato University School of 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