{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T11:34:53Z","timestamp":1768044893638,"version":"3.49.0"},"reference-count":46,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2013,4,1]],"date-time":"2013-04-01T00:00:00Z","timestamp":1364774400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2013,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Dental caries is one of the most prevalent infectious diseases in the United States, affecting approximately 80% of children and the majority of adults. Dental caries may lead to endodontic disease, where the bacterial infection progresses to the root canal system of the tooth, leading to periapical inflammation, bone erosion, severe pain, and tooth loss. Periapical inflammation may also exacerbate inflammation in other parts of the body. Although conventional clinical therapies for this disease are successful in approximately 80% of cases, there is still an urgent need for increased efficacy of treatment. In this study, we applied a novel gene-therapeutic approach using recombinant adeno-associated virus (AAV)-mediated Atp6i RNA interference (RNAi) knockdown of\n            <jats:italic>Atp6i\/TIRC7<\/jats:italic>\n            gene expression to simultaneously target periapical bone resorption and periapical inflammation. We found that\n            <jats:italic>Atp6i<\/jats:italic>\n            inhibition impaired osteoclast function\n            <jats:italic>in vitro<\/jats:italic>\n            and\n            <jats:italic>in vivo<\/jats:italic>\n            and decreased the number of T cells in the periapical lesion. Notably, AAV-mediated\n            <jats:italic>Atp6i\/TIRC7<\/jats:italic>\n            knockdown gene therapy reduced bacterial infection-stimulated bone resorption by 80% in the mouse model of endodontic disease. Importantly,\n            <jats:italic>Atp6i<\/jats:italic>\n            <jats:sup>+\/\u2212<\/jats:sup>\n            mice with haploinsufficiency of\n            <jats:italic>Atp6i<\/jats:italic>\n            exhibited protection similar to that in mice with bacterial infection-stimulated bone erosion and periapical inflammation, which confirms the potential therapeutic effect of AAV-small hairpin RNA (shRNA)-\n            <jats:italic>Atp6i\/TIRC7<\/jats:italic>\n            . Our results demonstrate that AAV-mediated\n            <jats:italic>Atp6i\/TIRC7<\/jats:italic>\n            knockdown in periapical tissues can inhibit endodontic disease development, bone resorption, and inflammation, indicating for the first time that this potential gene therapy may significantly improve the health of those who suffer from endodontic disease.\n          <\/jats:p>","DOI":"10.1128\/iai.00756-12","type":"journal-article","created":{"date-parts":[[2012,11,20]],"date-time":"2012-11-20T04:54:31Z","timestamp":1353387271000},"page":"1021-1030","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":27,"title":["RNA Interference-Mediated Silencing of\n            <i>Atp6i<\/i>\n            Prevents Both Periapical Bone Erosion and Inflammation in the Mouse Model of Endodontic Disease"],"prefix":"10.1128","volume":"81","author":[{"given":"Junqing","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA"},{"name":"Institute of Stomatology, Nanjing Medical University, Nanjing, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lijie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Disease, The Forsyth Institute, Cambridge, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Byron","family":"Tucker","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA"},{"name":"Department of Restorative Dentistry in Endodontics, Harvard School of Dental Medicine, Owings Mills, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guochun","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hajime","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Disease, The Forsyth Institute, Cambridge, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Stomatology, Nanjing Medical University, Nanjing, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongliang","family":"Ci","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongbing","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA"},{"name":"Institute of Stomatology, Nanjing Medical University, Nanjing, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip","family":"Stashenko","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Disease, The Forsyth Institute, Cambridge, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Ping","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","unstructured":"World Health Organization. 12 September 2012 date accessed. 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