Development of periodontal therapy by inhibiting neurotrophic inflammation via dopamine signaling

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K17065
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57030:Conservative dentistry-related
• Research Institution: Saitama Medical University
• Principal Investigator: Isozaki Yuta 埼玉医科大学, 医学部, 研究医員 (60828218)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: GE1細胞 / IL-17 / CXCL1 / ropinirole / D2受容体 / carrageenan / 歯周病 / haloperidol

Outline of Final Research Achievements

We explored whether the dopamine 2-like receptor agonist, ropinirole, suppresses neutrophilic inflammation and alveolar bone loss. We used a carrageenan-induced rat model of periodontitis with or without ropinirole. GE1 cells, the murine gingival epithelial cell line, were stimulated with carrageenan and IL-17A in the presence or absence of ropinirole. The effect of ropinirole was analyzed using RT-PCR and ELISA. Subsequently, in the carrageenan-induced rat model of periodontitis, alveolar bone resorption was observed in the maxillary second molar by μCT analysis, and ropinirole suppressed the alveolar bone destruction. The expression levels of CXCL1 and IL-17RA in GE1 cells were increased by carrageenan, and CXCL1 expression in GE1 cells was upregulated under IL-17A stimulation. Moreover, ropinirole inhibited CXCL1 and IL-17RA expression in GE1 cells in the presence of IL-17A and carrageenan. Finally, haloperidol promoted CXCL1 expression in GE1 cells in the presence of carrageenan.

Free Research Field

口腔外科学

Academic Significance and Societal Importance of the Research Achievements

本研究の結果で得られたD2様受容体アゴニストであるropiniroleがGE1細胞に作用して炎症を抑制するメカニズムは新たな知見であり、今後新たな歯周病治療薬開発の可能性を示している。今後はその他のD2様受容体アゴニストに加え、相反する作用を示すD1様受容体アゴニストやD2様受容体アンタゴニストを使用した研究を行うことでさらに意義のある研究になると考える。また、歯周病患者で局所と全身でTh17細胞の誘導およびdopamine濃度について検討することでD2様受容体アゴニストの局所投与と全身投与の方法に関して知見を得ることができ、新しい歯周病の治療法開発につながることが期待できる。