Regulation of bone metabolism by alternative splicing during osteoclast differentiation.

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K09053
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Tokyo University of Science
• Principal Investigator: Hayata Tadayoshi 東京理科大学, 薬学部生命創薬科学科, 准教授 (40420252)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 破骨細胞 / RNA結合タンパク質 / 核内構造体 / 骨粗鬆症 / 関節リウマチ

Outline of Final Research Achievements

We investigated the role of the RNA-binding protein Cpeb4 gene during osteoclast differentiation Cpeb4 gene expression was elevated during osteoclast differentiation, and the Cpeb4 protein was localized to the nuclear bodies via the PI3K / Akt signaling and the Nfatc1 activation pathway in a RANKL-dependent manner. Cpeb4 co-localized and interacted with the splicing factor in the nucleus. Osteoclast differentiation was inhibited in cells in which Cpeb4 was knocked down, and the expression of osteoclast differentiation-related genes was significantly reduced revealed by RNA-seq analysis. our results suggest that Cpeb4 is an RNA-binding protein essential for osteoclast differentiation, localizes to the nuclear structure in a RANKL-dependent manner, and may be involved in splicing events.

Free Research Field

骨代謝学

Academic Significance and Societal Importance of the Research Achievements

本研究成果は，骨や関節の病気における病態解明や、より効果的な治療薬の開発につながる可能性があり、ひいては今後の超高齢化社会における生活の質(QOL)の向上に寄与すると期待される。Cpeb4が破骨細胞分化を促進する詳細なメカニズムが今後さらに明らかになれば、骨粗鬆症や関節リウマチなどの骨や関節の病気の病態の解明につながり、さらにはこれらの病気に対する治療薬の開発が期待される。特に骨粗鬆症に悩む高齢者にとってQOLの向上につながる可能性があるのではないかと考えられる。