Development of inhibitors for Multiple Hereditary Exostoses

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09605
• 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: Saitama Medical University
• Principal Investigator: Mai Kuratani 埼玉医科大学, 医学部, 助手 (50758109)
• Co-Investigator(Kenkyū-buntansha): 片桐 岳信 埼玉医科大学, 医学部, 教授 (80245802)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 遺伝性疾患

Outline of Final Research Achievements

Multiple Hereditary Exostoses (MHE) is a genetic bone disease, which is characterized by growths of multiple osteochondromas. Patients with MHE carry a loss-of-function mutant of Ext1 and Ext2, which encodes a glycosyltransferase essential for heparan sulfate biosynthesis. In the present study, we established a new two types of in vitro experimental systems. The first is chondrocyte culture system that mimics the functional deletion of Ext1. The second is overexpression of mutant Ext1 in cultured cells. Our results suggest that the two experimental systems mimic the pathological condition of MHE. These are a useful model to examine the molecular mechanisms of mutant Ext1 and the potential therapeutics for MHE.

Free Research Field

病態生理学

Academic Significance and Societal Importance of the Research Achievements

本研究で樹立した解析法は、多発性外骨腫の発生機序解明と阻害薬の開発に応用できる可能性がある。