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 di...

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Published in:	Journal of periodontology (1970) Vol. 76; no. 2; pp. 229 - 233
Main Authors:	Ramamurthy, Nungavaram S., Greenwald, Robert A., Celiker, Mohamed Y., Shi, Eric Y.
Format:	Journal Article
Language:	English
Published:	737 N. Michigan Avenue, Suite 800, Chicago, IL 60611‐2690, USA American Academy of Periodontology 01-02-2005
Subjects:	Alveolar Bone Loss - metabolism Animal studies Animals Arthritis, Experimental - metabolism arthritis, rheumatoid/pathophysiology Biomarkers - metabolism cytokines Foot Genetic Therapy Gingiva - enzymology Interleukin-1 - metabolism Male Matrix Metalloproteinases - metabolism metalloproteinase, matrix periodontal diseases/pathophysiology Periodontitis - metabolism Plasmids Protease Inhibitors - metabolism Rats Rats, Inbred Lew Tissue Inhibitor of Metalloproteinase-4 Tissue Inhibitor of Metalloproteinases - biosynthesis Tissue Inhibitor of Metalloproteinases - genetics Tooth Mobility - metabolism Tumor Necrosis Factor-alpha - metabolism
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Summary:	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 <0.05) in untreated arthritic rats. All parameters improved after TIMP‐4 gene therapy. Conclusions: To our knowledge, this is the first study to report an association between experimental systemic arthritis in rats and elevated gingival tissue MMPs, cytokine levels, and periodontal disease. Reversal of these changes with TIMP‐4 gene therapy strengthens the pathophysiologic correlation between systemic and local disease. J Periodontol 2005;76:229‐233.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0022-3492 1943-3670
DOI:	10.1902/jop.2005.76.2.229