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However, this has not been experimentally demonstrated. We isolated and cultured human periodontal ligament stem cells (PDLSCs) from healthy and inflamed tissues. PDLSCs were treated with either inflammatory factors or nicotine. We measured expression of genes that are associated with osteogenic differentiation and osteoclast formation using RT\u2010qPCR and Western blot analyses. Besides, immunohistochemical staining, micro\u2010CT analysis and tartaric acid phosphatase staining were used to measure \u03b17 nAChR expression and function. Inflammation up\u2010regulated \u03b17 nAChR expression in both periodontal ligament tissues and PDLSCs. The up\u2010regulated \u03b17 nAChR contributed to the synergistic effect of nicotine and inflammation, leading to a decreased capability of osteogenic differentiation and increased capability of osteoclast formation\u2010induction of PDLSCs. Moreover, the inflammation\u2010induced up\u2010regulation of \u03b17 nAChR was partially dependent on the level of phosphorylated GSK\u20103\u03b2. This study provides experimental evidence for the pathological development of smoking\u2010related periodontitis and sheds new light on developing inflammation and \u03b17 nAChR\u2010targeted therapeutics to treat and prevent the disease.<\/jats:p>","DOI":"10.1111\/jcmm.14986","type":"journal-article","created":{"date-parts":[[2020,1,13]],"date-time":"2020-01-13T08:59:40Z","timestamp":1578905980000},"page":"2663-2676","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Inflammation has synergistic effect with nicotine in periodontitis by up\u2010regulating the expression of \u03b17 nAChR via phosphorylated GSK\u20103\u03b2"],"prefix":"10.1111","volume":"24","author":[{"given":"Zhifei","family":"Zhou","sequence":"first","affiliation":[{"name":"State Key Laboratory of Military Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; Shaanxi Clinical Research Center for Oral Diseases Department of 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