Glucose sensing in osteoclasts and the regulatory mechanism of their differentiation

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20998
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0907:Oral science and related fields
• Research Institution: Kyushu Dental College
• Principal Investigator: Yasuda Kazuma 九州歯科大学, 歯学部, 特別研修員 (10966641)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: 骨代謝 / 破骨細胞

Outline of Final Research Achievements

T1R1, T1R2, and T1R3 taste receptors monitor energy and nutritional status not only in the oral cavity but also in various tissues. It has been reported that mice with loss of T1R3 function show high bone mass, but the details remain unclear. In this study, we investigated the function of T1R3 in osteoclasts, and found that osteoclasts lacking T1R3 had reduced differentiation potential. On the other hand, overexpression of T1R3 promoted osteoclast differentiation, which was further enhanced by the addition of glucose or artificial sweeteners. Surprisingly, T1R3 may accept glucose as a homodimer of glucose and promote osteoclast differentiation via MAP kinase.

Free Research Field

小児歯科学

Academic Significance and Societal Importance of the Research Achievements

従来，舌を中心とした口腔内に発現し味感覚の受容を司るだけと思われていた味覚受容体が，破骨細胞にも発現し，その機能を明らかにすることができた本研究の価値は歯科領域だけにとどまらない．この学術的意味合いだけでなく，今後高血糖状態における骨吸収の活性化にT1R3が関与することを明らかにできれば，将来的にこれらT1R3は糖尿病や肥満における骨有害事象に対する治療標的になり得る．すなわち，T1R3は創薬のターゲットに適したGタンパク質共役型受容体であり， T1R3を治療標的とした骨代謝疾患治療薬開発に貢献できる可能性がある．