{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:18:04Z","timestamp":1784593084449,"version":"3.55.0"},"reference-count":47,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2015,6,11]],"date-time":"2015-06-11T00:00:00Z","timestamp":1433980800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH","award":["AR-44741"],"award-info":[{"award-number":["AR-44741"]}]},{"name":"NIH","award":["R01DE023813"],"award-info":[{"award-number":["R01DE023813"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Clinic Periodontology"],"published-print":{"date-parts":[[2015,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Periodontitis induced by oral pathogens leads to severe periodontal tissue damage and osteoclast\u2010mediated bone resorption caused by inflammation. On the basis of the importance of Ac45 in osteoclast formation and function, we performed this study to evaluate the therapeutic potential of periodontitis by local adeno\u2010associated virus (<jats:styled-content style=\"fixed-case\">AAV<\/jats:styled-content>)\u2010mediated Ac45 gene knockdown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and Methods<\/jats:title><jats:p>We used <jats:styled-content style=\"fixed-case\">AAV<\/jats:styled-content>\u2010mediated short hairpin <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>i knockdown of Ac45 gene expression (<jats:styled-content style=\"fixed-case\">AAV<\/jats:styled-content>\u2010sh\u2010Ac45) to inhibit bone erosion and gingival inflammation simultaneously in a well\u2010established periodontitis mouse model induced by <jats:italic>Porphyromonas gingivalis W50<\/jats:italic>. Histological studies were performed to evaluate the bone protection of <jats:styled-content style=\"fixed-case\">AAV<\/jats:styled-content>\u2010sh\u2010Ac45. Immunochemistry, <jats:styled-content style=\"fixed-case\">ELISA<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">qRT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> were performed to reveal the role of Ac45 knockdown on inflammation, immune response and expression of cytokine.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that Ac45 knockdown impaired osteoclast\u2010mediated extracellular acidification and bone resorption in\u00a0vitro <jats:italic>and<\/jats:italic> in\u00a0vivo. Furthermore, local administration of <jats:styled-content style=\"fixed-case\">AAV<\/jats:styled-content>\u2010sh\u2010Ac45 protected mice from bone erosion by &gt;85% and attenuated inflammation and decreased infiltration of T cells, dendritic cells and macrophages in the periodontal lesion. Notably, the expression of pro\u2010inflammatory cytokines was also reduced.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Local <jats:styled-content style=\"fixed-case\">AAV<\/jats:styled-content>\u2010sh\u2010Ac45 gene therapy efficiently protects against periodontal tissue damage and bone erosion through both inhibition of osteoclast function and attenuating inflammation, and may represent a powerful new treatment strategy for periodontitis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jcpe.12415","type":"journal-article","created":{"date-parts":[[2015,5,8]],"date-time":"2015-05-08T02:03:01Z","timestamp":1431050581000},"page":"599-608","source":"Crossref","is-referenced-by-count":17,"title":["Ac45 silencing mediated by <scp>AAV<\/scp>\u2010sh\u2010Ac45\u2010<scp>RNA<\/scp>i prevents both bone loss and inflammation caused by 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