2022 Fiscal Year Final Research Report
Role of GABA receptor rho2 (Gabrr2) and GABA C receptor agonist, TACA, in osteoclast differentiation.
| Project/Area Number |
20K09880
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 57010:Oral biological science-related
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| Research Institution | The University of Tokushima |
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Principal Investigator |
TAMAMURA Yoshihiro 徳島大学, 大学院医歯薬学研究部(医学域), 助教 (70431963)
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| Co-Investigator(Kenkyū-buntansha) |
山口 朗 東京歯科大学, 歯学部, 客員教授 (00142430)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | GABA受容体rho2 / 破骨細胞分化 / 骨芽細胞分化 |
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| Outline of Final Research Achievements |
Gabrr2 is a subunit of GABAc receptor that functions as a chloride ion channel, however its expression and function in osteoclast differentiation are largely unknown. In this study, we examined the expression and function of Gabrr2 in vitro using bone marrow-derived primary osteoclasts. Gabrr2 expression was upregulated in parallel with the expression of osteoclast differentiation marker genes. Retroviral overexpression of Gabrr2 or treatment with its agonist TACA resulted in the reduction of TRAP staining and the decereased expression of TRAP, Nfatc1 and Cathepsin K. In contrast, treatment with shGabrr2 enhanced expression of these genes. Moreover, upregulation of Nfatc1 by shGabrr2 was blunted by the treatment with calcineurin inhibitor FK506. Also, Gabrr2 overexpression resulted in the reduction of phospho-Ikba after TNF treatment. These results indicate that Gabrr2 has a inhibitory role for the osteoclast differentiation by inhibiting calcineurin activity or NFkB signaling.
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| Free Research Field |
骨軟骨代謝
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| Academic Significance and Societal Importance of the Research Achievements |
近年骨形成において、骨吸収を終えた破骨細胞から骨芽細胞へ骨形成開始の指令が出されるとうカップリングが注目されている。ずなわち、過度の破骨細胞分化抑制は、骨形成抑制につながる可能性があるため、骨芽細胞分化促進と破骨細胞分化抑制の両方の作用を併せ持つ分子が骨粗鬆症の理想的な治療標的と考えられる。本研究では、Gabrr2の破骨細胞抑制作用明らかにし、さらに、Gabrr2の骨骨粗鬆症の髄間質細胞の初期骨芽細胞分化に対する促進作用も明らかにした。これらのことからGabrr2が骨粗鬆症の理想的な治療標的となる可能性が考えられ、本研究は社会的意義が高いと考えられる。
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