Nordic Bioscience, Herlev, Denmark.
Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland.
Curr Opin Rheumatol. 2022 Jan 1;34(1):54-60. doi: 10.1097/BOR.0000000000000845.
Osteoarthritis (OA) is a painful disease for which drug development has proven difficult. One major reason for this is the heterogeneity of the disease and the current lack of operationalized means to distinguish various disease endotypes (molecular subtypes). Biomarkers measured in blood or urine, reflecting joint tissue turnover, have been developed and tested during the last decades. In this narrative review, we provide highlights on biomarkers derived from the two most studied and abundant cartilage proteins - type II collagen and aggrecan.
Multiple biomarkers assessing type II collagen degradation and formation, and aggrecan turnover have been developed. Several markers, such as uCTX-II, have been validated for their association with disease severity and prognosis, as well as pharmacodynamically used to describe the mode of action and efficacy of drugs in development. There is a great need for biomarkers for subdividing patients (i.e., endotyping) and recent scientific advances have not yet come closer to achieving this goal.
There is strong support for using biomarkers for understanding OA, reflecting degradation and formation of the joint tissues, focused on type II collagen and aggrecan. There is still a lack of in vitro diagnostics, in all contexts of use.
骨关节炎（OA）是一种痛苦的疾病，药物研发一直颇具难度。造成这一现象的一个主要原因是该疾病存在异质性，且目前缺乏用于区分各种疾病表型（分子亚型）的可操作手段。过去几十年来，人们已经开发并测试了可在血液或尿液中测量、反映关节组织更新的生物标志物。在本综述中，我们重点介绍了源自两种研究最多、含量最丰富的软骨蛋白——Ⅱ型胶原和聚集蛋白聚糖的生物标志物。
已经开发出了多种评估Ⅱ型胶原降解和形成以及聚集蛋白聚糖周转率的生物标志物。某些标志物，如 uCTX-II，已经通过其与疾病严重程度和预后的相关性得到验证，并且还被用于描述开发中药物的作用模式和疗效的药效学。目前迫切需要用于细分患者（即表型分型）的生物标志物，但最近的科学进展尚未更接近这一目标。
有强有力的证据支持使用生物标志物来了解 OA，这些标志物反映了关节组织的降解和形成，重点是Ⅱ型胶原和聚集蛋白聚糖。在所有使用情况下，体外诊断仍存在不足。
