Elucidation of the effect of Dscr1 on the gene expression regulation mechanism of osteoblasts

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K19287
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57070:Developmental dentistry-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Kasahara Yuki 東京医科歯科大学, 大学院医歯学総合研究科, 非常勤講師 (50822558)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: Dscr1 / 骨芽細胞 / ダウン症候群

Outline of Final Research Achievements

In this study, we focused on the calcineurin inhibitory activity of Down syndrome critical region 1 (Dscr1), encoded on chromosome 21, which is associated with Down syndrome. We investigated the impact of Dscr1 variant-specific expression dysregulation on bone metabolism. The experimental results revealed that the expression level of Dscr1.v2 protein increased with the elevation of intracellular cAMP concentration, suggesting its involvement in bone morphogenesis. Additionally, overexpression of Dscr1.v2 led to changes in calcification ability. However, attempts to identify the functional expression domain through stable expression of Dscr1 variants were unsuccessful, and no significant changes were observed in bone morphology analysis of Dscr1.v2 overexpressing transgenic mice.

Free Research Field

歯科矯正学

Academic Significance and Societal Importance of the Research Achievements

骨芽細胞におけるDscr1バリアント特異的な発現変調およびDscr1.v2の過剰発現が骨の代謝機能へ関連することが示唆されたことにより、ダウン症候群の骨形態形成不全に関する新たな理解、病態解明に向けた基礎研究の進展に寄与したと考える。また、ダウン症候群における治療法の開発に向けた基盤となるだけでなく、骨代謝異常や骨疾患の治療法の開発にも役立つ可能性がある。また、骨形成に関与するメカニズムの理解は、一般的な骨の健康管理にも応用できると考える。総じて、本研究はダウン症候群の病態解明に寄与するだけでなく、骨形態形成不全への治療法開発や骨の健康状態の向上に向けた展望を提供できたと考えられる。