摘要

  软骨代谢和周转是骨关节炎 (OA) 的标志，可以通过基于血液或尿液的细胞外基质蛋白 (ECMP) 降解标志物进行评估。 此类标志物的水平可反映疾病活动性，因此可用作药物开发中的药效标志物。 Aggrecan 是关节软骨的主要 ECMP，被 ADAMTS-5 降解，ADAMTS-5 在 OA 中被上调和激活。 充分描述的 ADAMTS-5 切割位点之一位于 G1-G2 全局域中的 373E-374A，导致 ARGS-G2 片段释放到滑液和循环中。 目的是表征用于定量 OA 患者血清中 374ARGS-G2 的人 ARGS (huARGS) 测定。

  Cartilage metabolism and turnover is a hallmark of Osteoarthritis (OA), and can be assessed by blood- or urine-based markers of extracellular matrix protein (ECMP) degradation. Levels of such markers may reflect disease activity and as such be applied in drug development as pharmacodynamic markers. Aggrecan, a major ECMP of articular cartilage, is degraded by ADAMTS-5, which is upregulated and activated in OA. One of the well-described ADAMTS-5 cleavage sites is at 373E-374A in the G1-G2 inter-global domain, resulting in the release of ARGS-G2 fragment to synovial fluid and circulation. The aim was to characterize the human ARGS (huARGS) assay for quantification of 374ARGS-G2 in serum of OA patients.

  https://www.oarsijournal.com/article/S1063-4584(20)30166-7/abstract