Protease-activated receptor-2 mediated colitis and alveolar bone metabolism

Previous reports have showed a higher incidence of osteoporosis in patients with inflammatory bowel disease (IBD), and suggest similarities in the immunopathogenesis of IBD and periodontitis. We made the hypothesis that activation of protease-activated receptor (PAR-2) in the gastrointestinal tract is involved in the common immunoinflammatory mechanisms associated with IBD-associated periodontitis.

Objectives: In the present study, we have investigated the effect of chronic intracolonic activation of PAR-2 on colonic inflammation and alveolar bone metabolism in mice.

Methods: C57Bl6 (WT) and PAR-2 deficient (PAR-2-/-) male mice were randomly assigned to receive intracolonic administration of one of the following treatments (8 animals/group): I) SLIGRL-NH2 (50µg/ day): selective agonist of PAR-2; II) LRGILS-NH2 (50µg/ day): control peptide not active on PAR-2; or III) 1.5mg trinitrobenzene sulfonic acid (TNBS). After 28 days, blood samples were collected and the level of serum alkaline phosphatase activity (ALP) was determined by ELISA. Colonic tissues were removed and the macroscopic damage scores (MDS), bowel thickness (BT), and myeloperoxidase activity (MPO) were analyzed. The alveolar bone mineral density (ABMD) was determined by a micro-CT system.

Results: SLIGRL-NH2 led to significantly (p<0.05) increased MPO activity in colonic tissues from WT animals compared to PAR-2-/- mice, and compared to WT mice receiving LRGILS-NH2 or TNBS treatments. In addition, SLIGRL-NH2 led to significantly (p<0.05) increased mean MDS and increased mean BT in colonic tissues from WT animals compared to PAR-2-/- mice, and compared to WT mice receiving LRGILS. No significant differences were found between SLIGRL-NH2 and TNBS treatments in WT mice. ALP and ABMD did not change among different experimental groups.

Conclusion: We have concluded that PAR-2 plays an important role in the pathogenesis of colonic inflammation, and that chronic experimental colitis has no significant effect on alveolar bone metabolism in mice.

External funding: Canadian Association of Gastroenterology (CAG)/CIHR Rx&D Fellowship Award.