{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,22]],"date-time":"2026-02-22T05:04:38Z","timestamp":1771736678684,"version":"3.50.1"},"reference-count":45,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2021,2,6]],"date-time":"2021-02-06T00:00:00Z","timestamp":1612569600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007225","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007225","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aap.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Periodontology"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Evidence demonstrates that the thrombomodulin (TM) lectin domain (TMD1) exerts anti\u2010inflammatory functions. Lipopolysaccharides derived from <jats:italic>Porphyromonas gingivalis<\/jats:italic> (<jats:italic>Pg<\/jats:italic>\u2010LPS) are considered a major pathogenic factor for chronic periodontitis, promoting inflammation, osteoclastogenesis and alveolar bone resorption. Herein, we aimed to evaluate the potential therapeutic effect of recombinant TMD1 (rTMD1) in suppression of <jats:italic>Pg<\/jats:italic>\u2010LPS\u2010induced osteoclastogenesis and periodontal bone loss.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In vitro, the effects of <jats:italic>Pg<\/jats:italic>\u2010LPS, tumor necrosis factor (TNF)\u2010\u03b1 and rTMD1 on osteoclast differentiation were investigated using receptor activator of nuclear factor\u2010\u03baB ligand (RANKL)\u2010stimulated RAW 264.7 macrophages. In vivo, the effects of rTMD1 treatment were evaluated in a model of experimental periodontitis induced by direct injection of <jats:italic>Pg<\/jats:italic>\u2010LPS into the vestibular gingiva.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Administration of <jats:italic>Pg<\/jats:italic>\u2010LPS to RANKL\u2010stimulated RAW 264.7 macrophages resulted in upregulation of <jats:italic>CD86<\/jats:italic> and osteoclast marker (eg, <jats:italic>Dc\u2010stamp<\/jats:italic> and <jats:italic>Trap<\/jats:italic>) gene expression and increase of pro\u2010inflammatory cytokine production (e.g., TNF\u2010\u03b1) during osteoclast differentiation, and rTMD1 can attenuate these effects. Also, rTMD1 inhibited <jats:italic>Pg<\/jats:italic>\u2010LPS\u2010enhanced in vitro bone resorption in a dose\u2010dependent manner. Moreover, TNF\u2010\u03b1 promoted phosphorylation of p38 and ERK during osteoclast differentiation, and the signal activation can be inhibited by rTMD1. Finally, treatment with rTMD1 hindered <jats:italic>Pg<\/jats:italic>\u2010LPS\u2010induced alveolar bone loss in experimental periodontitis in mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study demonstrated that rTMD1 attenuates <jats:italic>Pg<\/jats:italic>\u2010LPS\u2010enhanced M1 macrophage polarization, osteoclastogenesis and periodontal bone resorption and thus holds therapeutic promise for periodontitis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jper.20-0732","type":"journal-article","created":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T06:50:46Z","timestamp":1610693446000},"page":"1622-1634","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Recombinant thrombomodulin lectin\u2010like domain attenuates <i>Porphyromonas gingivalis<\/i> lipopolysaccharide\u2010induced osteoclastogenesis and periodontal bone resorption"],"prefix":"10.1002","volume":"92","author":[{"given":"Lan\u2010Yun","family":"Chang","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology College of Medicine National Cheng Kung University  Tainan Taiwan"},{"name":"Department of Surgery National Cheng Kung University Hospital College of Medicine National Cheng Kung University  Tainan Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1382-1495","authenticated-orcid":false,"given":"Chao\u2010Han","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology College of Medicine National Cheng Kung University  Tainan Taiwan"},{"name":"Department of Surgery National Cheng Kung University Hospital College of Medicine National Cheng Kung University  Tainan Taiwan"},{"name":"Department of Biostatistics Vanderbilt University Medical Center  Nashville 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