TREM-1 Is Upregulated in Experimental Periodontitis, and Its Blockade Inhibits IL-17A and RANKL Expression and Suppresses Bone loss.

AIM: Triggering receptor expressed on myeloid cells-1 (TREM-1) is a modifier of local and systemic inflammation. There is clinical evidence implicating TREM-1 in the pathogenesis of periodontitis. However, a cause-and-effect relationship has yet to be demonstrated, as is the underlying mechanism. The aim of this study was to elucidate the role of TREM-1 using the murine ligature-induced periodontitis model.

METHODS

A synthetic antagonistic LP17 peptide or sham control was microinjected locally into the palatal gingiva of the ligated molar teeth.

RESULTS

Mice treated with the LP17 inhibitor developed significantly less bone loss as compared to sham-treated mice, although there were no differences in total bacterial load on the ligatures. To elucidate the impact of LP17 on the host response, we analyzed the expression of a number of immune-modulating genes. The LP17 peptide altered the expression of 27/92 genes ≥ two-fold, but only interleukin (IL)-17A was significantly downregulated (4.9-fold). Importantly, LP17 also significantly downregulated the receptor activator of nuclear factor kappa-B-ligand (RANKL) to osteoprotegerin (OPG) ratio that drives osteoclastic bone resorption in periodontitis.

CONCLUSION

Our findings show for the first time that TREM-1 regulates the IL-17A-RANKL/OPG axis and bone loss in experimental periodontitis, and its therapeutic blockade may pave the way to a novel treatment for human periodontitis.