Chondrocyte glycome analysis reveals the pathogenesis of osteoarthritis

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K18516
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Hokkaido University
• Principal Investigator: Homan Kentaro 北海道大学, 医学研究院, 博士研究員 (40823331)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: グライコーム / 変形性関節症 / 軟骨変性 / 糖鎖解析

Outline of Final Research Achievements

Degeneration of cartilage, the main component of osteoarthritis (OA) lesions, is believed to begin with the destruction of glycan structures in proteoglycans. Although many studies on the pathogenesis of OA have focused on the hypertrophic differentiation of chondrocytes, none have addressed changes in glycoconjugate sugar chains. We have shown that N-glycans are altered before the appearance of histological changes in the cartilage matrix and that glycosphingolipids are involved in chondrocyte hypertrophy and OA progression. Therefore, in order to detect homologous glycan variation during cartilage tissue degeneration and chondrocyte differentiation, we succeeded in identifying glycans that play a important role in the onset of OA by performing qualitative and quantitative comparative analysis of glycan structural changes in all classes of glycans without limiting to one glycan class.

Free Research Field

整形外科学

Academic Significance and Societal Importance of the Research Achievements

糖鎖は同一のエピトープ構造にN-、O-結合型糖鎖、糖脂質などの異なるクラスの複合糖質を一塊として発現しており、あるクラスの糖鎖の合成不全が他の糖鎖で代償される可能性がある。軟骨変性や軟骨細胞の肥大分化の開始を理解するためには細胞全体が提示する糖鎖を網羅的に解析する必要がある。これまでグライコーム解析は時間や感度の問題から技術的に困難であったが、糖鎖の固相担体からの切断と同時に液体クロマトグラフィーや質量分析を用いて大規模かつ高速に糖鎖を解析できるグライコブロッティング法とピラゾロン試薬共存下にβ脱離反応を行う手法を確立することによってこの問題を克服した。