Experimental Arthritis in Rats Induces Biomarkers of Periodontitis Which Are Ameliorated by Gene Therapy With Tissue Inhibitor of Matrix Metalloproteinases

Background: Periodontal disease (PD) and rheumatoid arthritis (RA) share many common pathophysiologic features, but a clinical relationship between the two conditions remains controversial, in part because of the confounding effects of anti‐inflammatory drug therapy universally used in the latter disease. To further explore this issue, inflammatory arthritis was induced in rats to determine the effect on gingival biomarkers of inflammation and tissue destruction and to investigate the effect of a therapeutic intervention devoid of conventional anti‐inflammatory properties. Methods: Adjuvant arthritis (AA) was induced in Lewis male rats by injecting mycobacterium cell wall in complete Freund's adjuvant using standard techniques. One group of animals was treated by induction of systemic tissue inhibitor of matrix metalloproteinases (TIMP‐4). At 3 weeks, arthritis severity was recorded and both paw and gingival tissues were collected for matrix metalloproteinase activity (MMP) and cytokine analysis. In addition, the maxillary jaws were removed for assessment of periodontal bone loss. Results: The development of arthritis was associated with elevated joint tissue MMPs, tumor necrosis factor (TNF)‐α, and interleukin (IL)‐1β levels compared to control rats. In the gingival tissue of the untreated arthritic rats, gelatinase, collagenase, TNF‐α, and IL‐1β were also elevated compared to control rats. Periodontal bone loss and tooth mobility were also increased significantly (P