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However, the influence of PD on arthritis development remains unclear. This investigation was undertaken to determine the contribution of chronic PD to immune activation and development of joint inflammation using the collagen-induced arthritis (CIA) model.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>DBA1\/J mice orally infected with <jats:italic>Porphyromonas gingivalis<\/jats:italic> were administered with collagen II (CII) emulsified in complete Freund\u2019s adjuvant (CFA) or incomplete Freund\u2019s adjuvant (IFA) to induce arthritis. Arthritis development was assessed by visual scoring of paw swelling, caliper measurement of the paws, mRNA expression, paw micro-computed tomography (micro-CT) analysis, histology, and tartrate resistant acid phosphatase for osteoclast detection (TRAP)-positive immunohistochemistry. Serum and reactivated splenocytes were evaluated for cytokine expression.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>Mice induced for PD and\/or arthritis developed periodontal disease, shown by decreased alveolar bone and alteration of mRNA expression in gingival tissues and submandibular lymph nodes compared to vehicle. <jats:italic>P. gingivalis<\/jats:italic> oral infection increased paw swelling and osteoclast numbers in mice immunized with CFA\/CII. Arthritis incidence and severity were increased by <jats:italic>P. gingivalis<\/jats:italic> in mice that received IFA\/CII immunizations. Increased synovitis, bone erosions, and osteoclast numbers in the paws were observed following IFA\/CII immunizations in mice infected with <jats:italic>P gingivalis<\/jats:italic>. Furthermore, cytokine analysis showed a trend toward increased serum Th17\/Th1 ratios when <jats:italic>P. gingivalis<\/jats:italic> infection was present in mice receiving either CFA\/CII or IFA\/CII immunizations. Significant cytokine increases induced by <jats:italic>P. gingivalis<\/jats:italic> oral infection were mostly associated to Th17-related cytokines of reactivated splenic cells, including IL-1\u03b2, IL-6, and IL-22 in the CFA\/CII group and IL-1\u03b2, tumor necrosis factor-\u03b1, transforming growth factor-\u03b2, IL-6 and IL-23 in the IFA\/CII group.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusions<\/jats:title>\n                        <jats:p>Chronic <jats:italic>P. gingivalis<\/jats:italic> oral infection prior to arthritis induction increases the immune system activation favoring Th17 cell responses, and ultimately accelerating arthritis development. These results suggest that chronic oral infection may influence RA development mainly through activation of Th17-related pathways.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/ar4376","type":"journal-article","created":{"date-parts":[[2013,11,12]],"date-time":"2013-11-12T02:01:00Z","timestamp":1384221660000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":107,"title":["Porphyromonas gingivalis oral infection exacerbates the development and severity of collagen-induced arthritis"],"prefix":"10.1186","volume":"15","author":[{"given":"Julie Teresa","family":"Marchesan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth Ann","family":"Gerow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riley","family":"Schaff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrei Dan","family":"Taut","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung-Yun","family":"Shin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Sugai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Brand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Burberry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Jorns","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven Karl","family":"Lundy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Nu\u00f1ez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A","family":"Fox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William V","family":"Giannobile","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2013,11,12]]},"reference":[{"key":"4062_CR1","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1902\/jop.2011.100638","volume":"82","author":"JM Albandar","year":"2011","unstructured":"Albandar JM: Underestimation of periodontitis in NHANES surveys. 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