Basic research on nucleotide sugar metabolism to overcome diseases of the locomotor system

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K05932
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 42020:Veterinary medical science-related
• Research Institution: Iwate University
• Principal Investigator: Furuichi Tatsuya 岩手大学, 農学部, 教授 (30392103)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 糖ヌクレオチド / 腱 / 軟骨 / CANT1 / SLC35A3 / 運動器疾患

Outline of Final Research Achievements

The following functions of the two nucleotide sugar (NS)-related molecules (CANT1 and SLC35A3) in the locomotor system were demonstrated. (1) In the tendon of Cant1-KO mice, the collagen fibrils were larger, less rounded, and poorly assembled, and the content of dermatan sulfate was markedly reduced. These results indicate that CANT1 is involved in the construction of tendon collagen fibers by regulating dermatan sulfate synthesis. (2) Slc35a3-KO mice exhibited severe spinal dysplasia and died within hours after birth. In the growth plate cartilage of Slc35a3-KO mice, the extracellular space was drastically reduced, and the contents of glycosaminoglycan (GAG) were significantly decreased. These results indicate that SLC35A3 is involved in cartilage formation by regulating GAG synthesis.

Free Research Field

基礎獣医学

Academic Significance and Societal Importance of the Research Achievements

高齢化社会を迎えている日本では、運動器疾患が急増しており、その対策が急務となっている。糖鎖は運動器構成細胞の機能においても重要な働きを担っており、糖ヌクレオチド (Nucleotide sugar: NS) 代謝関連分子は運動器疾患治療薬の標的分子になり得る可能性を持っている。本研究によって腱の発生または恒常性維持に関わるNS関連分子としてCANT1、脊椎と軟骨形成に関わるNS関連分子としてSLC35A3を同定することができた。両分子の機能解析を継続し、NS代謝関連分子を標的とした創薬研究へと発展させていきたい。