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In\u00a0vivo, the therapeutic effects of KMUP\u20103 were evaluated in a model of experimental periodontitis induced by gingival ligature placement.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We reveal that KMUP\u20103 suppressed osteoclastogenesis, inducible nitric oxide synthase activation, and reduced nitric oxide production enhanced by <jats:italic>Pg<\/jats:italic>\u2010LPS in RANKL\u2010primed RAW264.7 cells while also decreasing TLR4\/NF\u2010\u03baB p65 pathway activation and decreased pro\u2010inflammatory cytokine production; moreover, <jats:italic>Pg<\/jats:italic>\u2010LPS promoted NLRP3 activation and exacerbated pyroptosis induction effects that were abolished by KMUP\u20103. Finally, KMUP\u20103 ameliorated alveolar bone loss and IL\u20101\u03b2 levels in the gingival crevicular fluid in the rat ligature periodontitis model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study demonstrated that KMUP\u20103 attenuates <jats:italic>Pg<\/jats:italic>\u2010LPS\u2010enhanced osteoclastogenesis and macrophage pyroptosis. Notably, KMUP\u20103 alleviates alveolar bone loss in experimental periodontitis rats and thus suggests its certain role in safeguarding against periodontal bone resorption.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jre.13393","type":"journal-article","created":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T03:16:09Z","timestamp":1740539769000},"page":"723-736","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Xanthine Derivative <scp>KMUP<\/scp>\u20103 Alleviates Periodontal Bone Resorption by Inhibiting Osteoclastogenesis and Macrophage Pyroptosis"],"prefix":"10.1111","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2324-9178","authenticated-orcid":false,"given":"Shang\u2010En","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Pharmacology, College of Medicine Kaohsiung Medical University  Kaohsiung 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