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Loss of resident periodontal ligament fibroblasts (PDLFs) has been a major challenge in the periodontal treatment. This study aimed to investigate the exact role of necroptotic cell death in periodontal diseases. Elevated levels of receptor-interacting protein serine-threonine kinases -1 (RIPK1), phosphorylated RIPK3, mixed lineage kinase domain-like protein (MLKL), phosphorylated MLKL and FLIP<jats:sub>L<\/jats:sub> were observed in gingival tissues collected from patients with untreated chronic periodontitis; whereas no difference in caspase 8 was observed between the periodontitis and healthy control group. In contrast to the high incidence of necroptotic cell death in monocytes during live <jats:italic>P. gingivalis<\/jats:italic> infection with a low multiplicity of infection (MOI), necroptosis was only observed in PDLFs with a high MOI. Priming PDLFs with frozen thawed monocytes enhanced proinflammatory responses to <jats:italic>P. gingivalis<\/jats:italic> infection; moreover, frozen thawed monocytes stimulation triggered RIPK1, RIPK3 and MLKL-mediated-necroptotic cell death in PDLFs. These results indicated that RIPK3 and MLKL-mediated-necroptotic cell death participated in the pathogenesis of periodontitis, and DAMPs released from monocytes after <jats:italic>P. gingivalis<\/jats:italic> stimulation by necroptosis triggered not only inflammatory responses, but also necroptosis of PDLFs.<\/jats:p>","DOI":"10.1038\/s41598-019-39721-1","type":"journal-article","created":{"date-parts":[[2019,2,27]],"date-time":"2019-02-27T11:27:43Z","timestamp":1551266863000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Loss of periodontal ligament fibroblasts by RIPK3-MLKL-mediated necroptosis in the progress of chronic periodontitis"],"prefix":"10.1038","volume":"9","author":[{"given":"J.","family":"Shi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,2,27]]},"reference":[{"key":"39721_CR1","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1080\/21505594.2015.1014266","volume":"6","author":"R Lopez","year":"2015","unstructured":"Lopez, R., Hujoel, P. & Belibasakis, G. 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