TREM-1 Blockage Attenuates Periodontal Bone Loss in Experimental Periodontitis

Objectives: Triggering receptor expressed on myeloid cells 1 (TREM-1) is a modifier of local and systemic inflammation. There is increasing evidence of a role of TREM-1 in the pathogenesis of periodontal diseases. However, there are no interventional studies to demonstrate its involvement in experimental periodontitis. The aim of this study was to investigate the effect of local TREM-1 inhibition in the progression of experimental periodontitis, as well as the expression of associated molecular markers in gingival tissue.
Methods: Specific pathogen-free C57BL/6 mice were used. To induce experimental periodontitis, a 5-0 silk ligature was tied around the maxillary left second molar for 5 days. To evaluate the relative role of TREM-1, its synthetic antagonistic peptide LP17 was microinjected locally into the palatal gingiva of the ligated site. Gingival tissue samples were harvested and analyzed by quantitative real-time PCR for the expression of TREM-1, interleukin (IL)-1β, receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG). Bacterial load on the ligatures was determined by anaerobic cultivation on blood agar plates.

Results: Five days after placement of ligatures, mice treated with LP17 developed significantly less bone loss, compared to untreated mice. Total bacterial counts on the recovered ligatures did not show significant differences between the study groups. Gingival tissue obtained from the ligated sites demonstrated a significant induction of TREM-1 expression after 5 days, which was reduced by 1/3 in the presence of the LP17 inhibitor. IL-1β expression followed a similar pattern to that of TREM-1. The RANKL/OPG ratio, a molecular determinant of bone resorption, was induced by 13.8-fold in the affected sites, and was reduced to 5.1-fold in presence of LP17.
Conclusions: The present data indicate that TREM-1 is induced during the course of experimental periodontitis and contributes to inflammatory bone loss. This is the first proof-of-concept evidence implicating TREM-1 as a potential therapeutic target for the treatment of periodontitis.