Analysis of regulatory mechanisms for differentiation of human cartilage tissue

2022 Fiscal Year Final Research Report

• Project/Area Number: 18H02923
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Osaka University (2022); Kyoto University (2018-2021)
• Principal Investigator: Tsumaki Noriyuki 大阪大学, 大学院生命機能研究科, 教授 (50303938)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Keywords: 軟骨 / 椎間板髄核 / iPS細胞 / 内軟骨性骨化 / 細胞分化

Outline of Final Research Achievements

Research using genetically modified mice has contributed to understanding mechanisms that regulate chondrocyte differentiation. However, the extent to which findings obtained from mouse experiments works in human tissues has not been well known. To understand molecular mechanisms that regulate differentiation of chondrocytes in human tissues, we analyzed differentiation of cells in human iPS cell-derived cartilage that were subjected various conditions. We created cartilage from iPS cells from primates including human. The cartilage was analyzed under the conditions such as transplantation into articular cartilage defects, transplantation into bone defects, transplantation into nucleotomized spaces in intervertebral discs, and endochondral bone formation. The findings obtained in the research contribute to understanding molecular mechanisms that regulate differentiation of human chondrocytes in tissue.

Free Research Field

骨・軟骨代謝学　再生治療学

Academic Significance and Societal Importance of the Research Achievements

ほとんどの骨格組織は、内軟骨性骨化によって発生・成長し、維持される。成長軟骨の異常は骨格の変形と短縮の原因となり、骨系統疾患を引き起こす。また、関節軟骨の異常は運動障害を引き起こす。これらの疾患の病態を理解し、治療方法を開発するには、ヒト軟骨の分化制御機構を組織のレベルで理解する必要がある。本研究ではヒトiPS細胞由来軟骨を種々の条件下で解析しシングルセルRNAシーケンスを用いた網羅的探索を行うことにより、ヒト軟骨細胞の分化を制御する機構の一つを分子レベルで解析した。本成果は、難治性軟骨疾患の病態解析と創薬研究を行う上での基盤的知識になりうると考える。