Homan Kentaro, Onodera Tomohiro, Hanamatsu Hisatoshi, Furukawa Jun-Ichi, Momma Daisuke, Matsuoka Masatake, Iwasaki Norimasa
Department of Orthopaedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Institute for Glyco‑core Research (iGCORE), Nagoya University, Nagoya, Japan.
Elife. 2024 Mar 11;12:RP92275. doi: 10.7554/eLife.92275.
This study aimed to investigate the glycan structural changes that occur before histological degeneration in osteoarthritis (OA) and to determine the mechanism by which these glycan conformational changes affect cartilage degeneration. An OA model was established in rabbits using mannosidase injection, which reduced high-mannose type N-glycans and led to cartilage degeneration. Further analysis of glycome in human OA cartilage identified specific corefucosylated N-glycan expression patterns. Inhibition of N-glycan corefucosylation in mice resulted in unrecoverable cartilage degeneration, while cartilage-specific blocking of corefucosylation led to accelerated development of aging-associated and instability-induced OA models. We conclude that α1,6 fucosyltransferase is required postnatally to prevent preosteoarthritic deterioration of articular cartilage. These findings provide a novel definition of early OA and identify glyco-phenotypes of OA cartilage, which may distinguish individuals at higher risk of progression.
本研究旨在调查骨关节炎(OA)组织学退变之前发生的聚糖结构变化,并确定这些聚糖构象变化影响软骨退变的机制。通过注射甘露糖苷酶在兔中建立OA模型,该模型减少了高甘露糖型N-聚糖并导致软骨退变。对人OA软骨中糖组的进一步分析确定了特定的核心岩藻糖基化N-聚糖表达模式。抑制小鼠中的N-聚糖核心岩藻糖基化会导致不可恢复的软骨退变,而软骨特异性阻断核心岩藻糖基化会导致衰老相关和不稳定诱导的OA模型加速发展。我们得出结论,出生后需要α1,6岩藻糖基转移酶来预防关节软骨的骨关节炎前期退变。这些发现为早期OA提供了新的定义,并确定了OA软骨的糖表型,这可能有助于区分进展风险较高的个体。