{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T12:43:28Z","timestamp":1782823408937,"version":"3.54.5"},"reference-count":41,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,2,7]],"date-time":"2019-02-07T00:00:00Z","timestamp":1549497600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81300884"],"award-info":[{"award-number":["81300884"]}],"id":[{"id":"10.13039\/501100001809","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":[[2019,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Periodontitis, an oral inflammatory disease caused by periodontal pathogen infection, is the most prevalent chronic inflammatory disease and a major burden on healthcare. The TAM receptor tyrosine kinases (Tyro3, Axl and Mertk) and their ligands (Gas6 and Pros1) play a pivotal role in the resolution of inflammation and have been associated with chronic inflammatory and autoimmune diseases. In this study, we evaluated the effects of exogenous Pros1 in in vitro and in vivo models of periodontitis. We detected higher Pros1 but lower Tyro3 levels in inflamed gingival specimens of periodontitis patients compared with healthy controls. Moreover, Pros1 was mostly localized in the gingival epithelium of all specimens. In cultured human gingival epithelial cells (hGECs), <jats:italic>Porphyromonas gingivalis<\/jats:italic> LPS (<jats:italic>p.g<\/jats:italic>\u2010LPS) stimulation down\u2010regulated Pros1 and Tyro3. Exogenous Pros1 inhibited <jats:italic>p.g<\/jats:italic>\u2010LPS\u2013induced production of TNF\u2010\u03b1, IL\u20106, IL\u20101\u03b2, MMP9\/2 and RANKL in a Tyro3\u2010dependent manner as revealed by PCR, Western blot analysis, ELISA and gelatin zymography. Pros1 also restored Tyro3 expression down\u2010regulated by <jats:italic>p.g<\/jats:italic>\u2010LPS in hGECs. In rats treated with ligature and <jats:italic>p.g<\/jats:italic>\u2010LPS, administration of Pros1 attenuated periodontitis\u2010associated gingival inflammation and alveolar bone loss. Our mechanistic studies implicated SOCS1\/3 and STAT1\/3 as mediators of the in vitro and in vivo anti\u2010inflammatory effects of Pros1. Collectively, the findings from this work supported Pros1 as a novel anti\u2010inflammatory therapy for periodontitis.<\/jats:p>","DOI":"10.1111\/jcmm.14183","type":"journal-article","created":{"date-parts":[[2019,2,7]],"date-time":"2019-02-07T09:44:43Z","timestamp":1549532683000},"page":"2769-2781","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["The Pros1\/Tyro3 axis protects against periodontitis by modulating STAT\/SOCS signalling"],"prefix":"10.1111","volume":"23","author":[{"given":"Lei","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Stomatology, Changzheng Hospital Second Military Medical University Shanghai P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao Qing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Changzheng Hospital Second Military Medical University Shanghai P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming Jing","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Changzheng Hospital Second Military Medical University Shanghai P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wai","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Changzheng Hospital Second Military Medical University Shanghai P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Changzheng Hospital Second Military Medical University Shanghai P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun Fu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Changzheng Hospital Second Military Medical University Shanghai P. R. 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