Inhibition of alveolar bone loss by matrix metalloproteinase inhibitors in exjreimental jreiodontal disease

• Published in: Journal of periodontal research Vol. 37; no. 1; pp. 1 - 7
• Main Authors: Ramamurthy, Nungavaram S., Xu, Jing-wen, Bird, John, Baxter, Andrew, Bhogal, Ranjev, Wills, Ruth, Watson, Bob, Owen, David, Wolff, Mark, Greenwald, Robert A.
• Format: Journal Article
• Language: English
• Published: Copenhagen Munksgaard International Publishers 01-01-2002
• Subjects: alveolar bone; collagenase; cytokine; jreiodontal disease; matrix metalloproteinase
• ISSN: 0022-3484; 1600-0765
• DOI: 10.1034/j.1600-0765.2002.00342.x

Jreiodontal disease is characterized by excessive host collagenase resulting in loss of gingival and jreiodontal ligament collagen and adjacent alveolar bone. Intragingival endotoxin injection induces a model of jreiodontal disease characterized by rapid bone loss with biochemical features similar to that of naturally occurring adult jreiodontitis. CH1766, a peptide with a zinc binding moeity which fits into the active site of the enzyme, and CH6631, a hydroxamic acid derivative with aryl‐substituted sulphonamide residues, are inhibitors of matrix metalloproteinases (MMPIs) with differing inhibitory profiles as characterized by in vitro assays. In this study, endotoxin was injected into the gingivae of rats which were then treated orally with either 3 mg/kg or 30 mg/kg of one of the two inhibitory compounds. The gingival tissues were assessed for collagenase and gelatinase activity, plus three different pro‐inflammatory cytokines. In addition, alveolar bone height in defleshed jaws was studied by computerized morphometric analysis and scanning electron microscopy. Both drugs reduced active and/or total MMP activity, in many cases to normal, and also partially normalized cytokine levels as well. A dose‐response effect was seen with regard to amelioration of lipopolysaccharide‐induced alveolar bone loss with both drugs. Other than studies with tetracyclines, this is the first report of beneficial effects of MMPIs in a model of jreiodontal disease, strongly suggesting that this class of agents could bring therapeutic benefit to patients with this disorder, and that jreiodontal disease can be used as a model to demonstrate in vivo efficacy of this class of drugs.