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Here, we demonstrate that ovariectomy induces the T\u2010cell co\u2010stimulatory cytokine LIGHT, which stimulates both osteoblastogenesis and osteoclastogenesis by modulating osteoclastogenic cytokine expression, including TNF, osteoprotegerin, and the receptor activator of nuclear factor\u2010\u03baB ligand (RANKL). Predictably, LIGHT\u2010deficient (<jats:italic>Tnfsf14<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>) mice are protected from ovariectomy\u2010dependent bone loss, whereas trabecular bone mass increases in mice deficient in both LIGHT and T and B lymphocytes (<jats:italic>Rag<\/jats:italic><jats:sup>\n<jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup><jats:italic>Tnfsf14<\/jats:italic><jats:sup>\n<jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup>) and is associated with an inversion of the TNF and RANKL\/OPG ratio. Furthermore, women with postmenopausal osteoporosis display high levels of LIGHT in circulating T cells and monocytes. Taken together, these results indicate that LIGHT mediates bone loss induced by ovariectomy, suggesting that patients with postmenopausal osteoporosis may benefit from LIGHT antagonism. \u00a9 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.5385","type":"journal-article","created":{"date-parts":[[2020,1,28]],"date-time":"2020-01-28T07:42:33Z","timestamp":1580197353000},"page":"440-451","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["LIGHT\/TNFSF14 regulates estrogen deficiency\u2010induced bone loss"],"prefix":"10.1002","volume":"250","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0681-1432","authenticated-orcid":false,"given":"Giacomina","family":"Brunetti","sequence":"first","affiliation":[{"name":"Department of Basic and Medical Sciences, Neurosciences and Sense Organs, Section of Human Anatomy and Histology University of Bari  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppina","family":"Storlino","sequence":"additional","affiliation":[{"name":"Department of Emergency and Organ Transplantation, Section of Human Anatomy and Histology University of Bari  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Oranger","sequence":"additional","affiliation":[{"name":"Department of Emergency and Organ Transplantation, Section of Human Anatomy and Histology University of Bari  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graziana","family":"Colaianni","sequence":"additional","affiliation":[{"name":"Department of Emergency and Organ Transplantation, Section of Human Anatomy and Histology University of Bari  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria F","family":"Faienza","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science and Human Oncology, Paediatric Unit University of Bari  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Ingravallo","sequence":"additional","affiliation":[{"name":"Department of Emergency and Organ Transplantation, Pathology Section University of Bari  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariasevera","family":"Di Comite","sequence":"additional","affiliation":[{"name":"Department of Basic and Medical Sciences, Neurosciences and Sense Organs, Section of Human Anatomy and Histology University of Bari  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janne E","family":"Reseland","sequence":"additional","affiliation":[{"name":"Department of Biomaterials, Institute for Clinical Dentistry University of Oslo  Blindern Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Celi","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Traumatology Tor Vergata University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umberto","family":"Tarantino","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Traumatology Tor 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