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Tenomodulin (<jats:italic>Tnmd<\/jats:italic>) is a tendon\/ligament\u2010specific marker and anti\u2010angiogenic factor with abundant expression in the IVD. It is still unclear whether Tnmd contributes to the maintenance of IVD homeostasis, acting to inhibit vascular ingrowth into this normally avascular tissue. Herein, we investigated whether IVD degeneration could be induced spontaneously by the absence of <jats:italic>Tnmd<\/jats:italic>. Our results showed that Tnmd was expressed in an age\u2010dependent manner primarily in the outer annulus fibrous (OAF) and it was downregulated at 6\u00a0months of age corresponding to the early IVD degeneration stage in mice. <jats:italic>Tnmd<\/jats:italic> knockout (<jats:italic>Tnmd<\/jats:italic><jats:sup>\u2212<\/jats:sup><jats:italic><jats:sup>\/<\/jats:sup><\/jats:italic><jats:sup>\u2212<\/jats:sup>) mice exhibited more rapid progression of age\u2010related IVD degeneration. These signs include smaller collagen fibril diameter, markedly lower compressive stiffness, reduced multiple IVD\u2010 and tendon\/ligament\u2010related gene expression, induced angiogenesis, and macrophage infiltration in OAF, as well as more hypertrophic\u2010like chondrocytes in the nucleus pulposus. In addition, <jats:italic>Tnmd<\/jats:italic> and chondromodulin I (<jats:italic>Chm1<\/jats:italic>, the only homologous gene to <jats:italic>Tnmd<\/jats:italic>) double knockout (<jats:italic>Tnmd<\/jats:italic><jats:sup>\u2212<\/jats:sup><jats:italic><jats:sup>\/<\/jats:sup><\/jats:italic><jats:sup>\u2212<\/jats:sup><jats:italic>Chm1<\/jats:italic><jats:sup>\u2212<\/jats:sup><jats:italic><jats:sup>\/<\/jats:sup><\/jats:italic><jats:sup>\u2212<\/jats:sup>) mice displayed not only accelerated IVD degeneration, but also ectopic bone formation of IVD. Lastly, the absence of <jats:italic>Tnmd<\/jats:italic> in OAF\u2010derived cells promoted p65 and matrix metalloproteinases upregulation, and increased migratory capacity of human umbilical vein endothelial cells. In sum, our data provide clear evidences that Tnmd acts as\u00a0an angiogenic inhibitor in the IVD homeostasis and protects against age\u2010related IVD degeneration. Targeting Tnmd may represent a novel therapeutic strategy for attenuating age\u2010related IVD degeneration.<\/jats:p>","DOI":"10.1111\/acel.13091","type":"journal-article","created":{"date-parts":[[2020,2,21]],"date-time":"2020-02-21T16:41:26Z","timestamp":1582303286000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Loss of tenomodulin expression is a risk factor for age\u2010related intervertebral disc degeneration"],"prefix":"10.1111","volume":"19","author":[{"given":"Dasheng","family":"Lin","sequence":"first","affiliation":[{"name":"Experimental Surgery and Regenerative Medicine Clinic for General, Trauma and Reconstructive Surgery Ludwig\u2010Maximilians\u2010University (LMU) Munich Germany"},{"name":"Orthopaedic Center of People\u2019s Liberation Army The Affiliated Southeast Hospital of Xiamen University Zhangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Alberton","sequence":"additional","affiliation":[{"name":"Experimental Surgery and Regenerative Medicine Clinic for General, Trauma and Reconstructive Surgery Ludwig\u2010Maximilians\u2010University (LMU) Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Delgado Caceres","sequence":"additional","affiliation":[{"name":"Experimental Trauma Surgery Department of Trauma Surgery University Regensburg Medical Centre Regensburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carina","family":"Prein","sequence":"additional","affiliation":[{"name":"Center for Applied Tissue Engineering and Regenerative Medicine (CANTER) Munich University of Applied Sciences and Center for Nanoscience (CeNS) Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hauke","family":"Clausen\u2010Schaumann","sequence":"additional","affiliation":[{"name":"Center for Applied Tissue Engineering and Regenerative Medicine (CANTER) Munich University of Applied Sciences and Center for Nanoscience (CeNS) Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Zhongshan Hospital Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Attila","family":"Aszodi","sequence":"additional","affiliation":[{"name":"Experimental Surgery and Regenerative Medicine Clinic for General, Trauma and Reconstructive Surgery Ludwig\u2010Maximilians\u2010University (LMU) Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chisa","family":"Shukunami","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry Graduate School of Biomedical &amp; Health Sciences Hiroshima University Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James C","family":"Iatridis","sequence":"additional","affiliation":[{"name":"Leni and Peter W. May Department of Orthopaedics Icahn School of Medicine at Mount Sinai New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7588-1290","authenticated-orcid":false,"given":"Denitsa","family":"Docheva","sequence":"additional","affiliation":[{"name":"Experimental Trauma Surgery Department of Trauma Surgery University Regensburg Medical Centre Regensburg 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