Elucidation of the regulatory mechanism of osteoblast differentiation based on a new concept and development of therapeutic agents for cleidocranial dysplasia.

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K10063
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57010:Oral biological science-related
• Research Institution: Tokyo Dental College
• Principal Investigator: Saito Akiko 東京歯科大学, 歯学部, 助教 (90722835)
• Co-Investigator(Kenkyū-buntansha): 小野寺 晶子 東京歯科大学, 歯学部, 講師 (90637662)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 骨芽細胞分化 / RUNX2 / 疾患特異的iPS細胞

Outline of Final Research Achievements

We investigated a novel regulatory mechanism of osteoblast differentiation by RUNX2 using iPS cells derived from a patient with clavicular skull dysplasia who had a heterozygous mutation in RUNX2, a master transcription factor for osteoblast differentiation. The results suggest that RUNX2 regulates the expression of genes involved in osteoblast differentiation during osteoblast differentiation from iPS cells by regulating the expression of nuclear membrane proteins to maintain normal nuclear morphology, as well as the normal function of Lamin A and chromatin binding.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

骨芽細胞分化におけるRUNX2による核形態の維持は、その後の骨芽細胞分化に関わる遺伝子発現制御が正常に行われるために重要であると考えられた。これにより、RUNX2遺伝子変異に起因する鎖骨頭蓋骨異形成症（CCD)において、核膜タンパク質の異常によって引き起こされる疾患であるラミノパチーで使用される治療薬がCCDでも応用可能か検討できる。