Inhibition of sphingosine-1-phosphate receptor 2 attenuated ligature-induced periodontitis in mice

Objectives: Periodontitis is an inflammatory bone loss disease initiated by oral bacterial inflammation. Herein, we determined whether inhibition of sphingosine-1-phosphate receptor 2 (S1PR2, a G protein-coupled receptor) by its specific antagonist, JTE013, could alleviate ligature-induced periodontitis in mice.

Materials and methods: C57BL/6 mice were placed with silk ligatures at the left maxillary second molar to induce experimental periodontitis. Mice were treated with JTE013 or control vehicle (dimethyl sulfoxide, DMSO) oral topically on the ligatures once daily. After 15 days of treatment, RNA was extracted from the lingual mucosal tissues to quantify IL-1β, IL-6, and TNF mRNA levels in the tissues. Alveolar bone loss was determined by micro-computed tomography. Sagittal periodontal tissue sections were cut and stained by hematoxylin and eosin (H&E) for general histology, or stained by tartrate-resistant acid phosphatase (TRAP) for osteoclasts.

Results: Treatment with JTE013 attenuated ligature-induced alveolar bone loss compared with DMSO treatment. Treatment with JTE013 reduced IL-1β, IL-6, and TNF mRNA levels in murine gingival mucosal tissues, inhibited leukocyte infiltration in the periodontal tissues, and decreased the number of osteoclasts in the periodontal tissues compared with controls.

Conclusion: Oral topical administration of JTE013 alleviated periodontal inflammatory bone loss induced by ligature placement in mice.