Targeting the succinate receptor effectively inhibits periodontitis

Area of Science:

• Oral biology
• Immunology
• Microbiology

Background:

• Periodontal disease (PD) is a common inflammatory condition linked to oral microbial imbalance.
• Inflammation and bone loss are key features of severe PD.
• The role of specific metabolites in PD pathogenesis is an area of active research.

Purpose of the Study:

• To investigate the role of succinate and its receptor, SUCNR1, in the development and progression of periodontal disease.
• To explore the therapeutic potential of targeting the succinate-SUCNR1 pathway.

Main Methods:

• Quantification of succinate levels in subgingival plaque from PD patients.
• Detection of SUCNR1 expression in human and mouse periodontium.
• Utilizing mouse models of periodontitis with and without SUCNR1, and administration of succinate or a SUCNR1 antagonist.
• In vitro studies assessing inflammatory events and osteoclastogenesis.

Main Results:

• Abnormal elevation of succinate was found in subgingival plaque of severe PD subjects.
• SUCNR1 expression was detected in the periodontium.
• Exogenous succinate exacerbated periodontal disease in mice.
• SUCNR1 knockout mice showed protection against inflammation and bone loss in periodontitis models.
• A SUCNR1 antagonist inhibited inflammation and osteoclastogenesis in vitro and reduced bone loss in vivo.

Conclusions:

• Succinate-SUCNR1 axis plays a significant role in periodontitis pathogenesis.
• Targeting SUCNR1 with an antagonist presents a promising therapeutic strategy for periodontal disease.