Novel mechanism leading to the death of hypertrophic chondrocytes in endochondral ossification through the regulation of CCN2 expression

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K19232
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Okayama University
• Principal Investigator: MURASE Yurika 岡山大学, 大学病院, 医員 (70803708)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: CCN2 / 軟骨 / 細胞死 / ROS / 内軟骨性骨化

Outline of Final Research Achievements

The aim of this study was to investigate a novel mechanism that leads to the death of hypertrophic chondrocytes in endochondral ossification through the regulation of CCN2 expression. We found that CCN2 expression was up-regulated in low-concentration H2O2-treated chondrocytes but was down-regulated in high-concentration H2O2-treated ones. CCN2-silencing in chondrocytes induced apoptosis, and the induction of apoptosis was suppressed by a ROS inhibitor. These results suggest that CCN2 expression may be up-regulated by intracellular ROS rising during chondrocyte differentiation but finally down-regulated and thereby hypertrophic chondrocytes lead to ROS-mediated apoptosis.

Free Research Field

外科系歯学

Academic Significance and Societal Importance of the Research Achievements

学術的意義：本研究により、内軟骨性骨化の最終段階―肥大軟骨細胞の細胞死誘導メカニズムの一端を解明する成果が生み出された。
社会的意義：本研究により、骨・軟骨形成に異常をきたす疾病の原因・病態究明、治療法開発につながる成果が生み出された。