{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:35:03Z","timestamp":1790696103916,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,1,11]],"date-time":"2016-01-11T00:00:00Z","timestamp":1452470400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100008333","name":"University of Alabama at Birmingham","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008333","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Periodontal Research"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:sec><jats:title>Background and Objective<\/jats:title><jats:p>Periodontitis is a severe chronic inflammatory disease and one of the most prevalent non\u2010communicable chronic diseases that affects the majority of the world's adult population. While great efforts have been devoted toward understanding the pathogenesis of periodontitis, there remains a pressing need for developing potent therapeutic strategies for targeting this dreadful disease. In this study, we utilized adeno\u2010associated virus (<jats:styled-content style=\"fixed-case\">AAV<\/jats:styled-content>) expressing cathepsin K (Ctsk) small hairpin (sh)<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">AAV<\/jats:styled-content>\u2010sh\u2010Ctsk) to silence Ctsk <jats:italic>in vivo<\/jats:italic> and subsequently evaluated its impact in periodontitis as a potential therapeutic strategy for this disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and Methods<\/jats:title><jats:p>We used a known mouse model of periodontitis, in which wild\u2010type <jats:styled-content style=\"fixed-case\">BALB<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">cJ<\/jats:styled-content> mice were infected with <jats:italic>Porphyromonas gingivalis<\/jats:italic> W50 in the maxillary and mandibular periodontium to induce the disease. <jats:styled-content style=\"fixed-case\">AAV<\/jats:styled-content>\u2010sh\u2010Ctsk was then administrated locally into the periodontal tissues <jats:italic>in vivo<\/jats:italic>, followed by analyses to assess progression of the disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">AAV<\/jats:styled-content>\u2010mediated Ctsk silencing drastically protected mice (&gt; 80%) from <jats:italic>P. gingivalis<\/jats:italic>\u2010induced bone resorption by osteoclasts. In addition, <jats:styled-content style=\"fixed-case\">AAV<\/jats:styled-content>\u2010sh\u2010Ctsk administration drastically reduced inflammation by impacting the expression of many inflammatory cytokines as well as T\u2010cell and dendritic cell numbers in periodontal lesions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">AAV<\/jats:styled-content>\u2010mediated Ctsk silencing can simultaneously target both the inflammation and bone resorption associated with periodontitis through its inhibitory effect on immune cells and osteoclast function. Thereby, <jats:styled-content style=\"fixed-case\">AAV<\/jats:styled-content>\u2010sh\u2010Ctsk administration can efficiently protect against periodontal tissue damage and alveolar bone loss, establishing this <jats:styled-content style=\"fixed-case\">AAV<\/jats:styled-content>\u2010mediated local silencing of Ctsk as an important therapeutic strategy for effectively treating periodontal disease.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jre.12345","type":"journal-article","created":{"date-parts":[[2016,1,12]],"date-time":"2016-01-12T05:04:37Z","timestamp":1452575077000},"page":"647-660","source":"Crossref","is-referenced-by-count":43,"title":["The silencing of cathepsin K used in gene therapy for periodontal disease reveals the role of cathepsin K in chronic infection and inflammation"],"prefix":"10.1111","volume":"51","author":[{"given":"W.","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pathology University of Alabama at Birmingham Birmingham AL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Alabama at Birmingham Birmingham AL USA"},{"name":"The State Key Laboratory of Oral Diseases West China College of Stomatology Sichuan University Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Alabama at Birmingham Birmingham AL USA"},{"name":"The State Key Laboratory of Oral Diseases West China College of Stomatology Sichuan University Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Alabama at Birmingham Birmingham AL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Jules","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Alabama at Birmingham Birmingham AL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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