Dr. Rolf M. Schwiete Research Unit for Osteoarthritis, Department of Orthopedics (Friedrichsheim), University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany.
Am J Physiol Cell Physiol. 2023 Feb 1;324(2):C377-C394. doi: 10.1152/ajpcell.00464.2022. Epub 2022 Dec 26.
Osteoarthritis (OA) is among the most frequent diseases of the musculoskeletal system. Degradation of cartilage extracellular matrix (ECM) is a hallmark of OA. During the degradation process, intact/full-length proteins and proteolytic fragments are released which then might induce different downstream responses via diverse receptors, therefore leading to different biological consequences. Collagen type II and the proteoglycan aggrecan are the most abundant components of the cartilage ECM. However, over the last decades, a large number of minor components have been identified and for some of those, a role in the manifold processes associated with OA has already been demonstrated. To date, there is still no therapy able to halt or cure OA. A better understanding of the matrikine landscape occurring with or even preceding obvious degenerative changes in joint tissues is needed and might help to identify molecules that could serve as biomarkers, druggable targets, or even be blueprints for disease modifying drug OA drugs. For this narrative review, we screened PubMed for relevant literature in the English language and summarized the current knowledge regarding the function of selected ECM molecules and the derived matrikines in the context of cartilage and OA.
骨关节炎(OA)是最常见的肌肉骨骼系统疾病之一。软骨细胞外基质(ECM)的降解是 OA 的一个标志。在降解过程中,完整/全长蛋白和蛋白水解片段被释放,然后通过不同的受体诱导不同的下游反应,从而导致不同的生物学后果。II 型胶原和蛋白聚糖聚集素是软骨 ECM 中最丰富的成分。然而,在过去的几十年里,已经鉴定出大量的次要成分,其中一些已经证明在与 OA 相关的多种过程中发挥作用。迄今为止,仍然没有能够阻止或治愈 OA 的疗法。需要更好地了解基质细胞因子景观,这些景观可能与关节组织中明显的退行性变化同时发生,甚至早于退行性变化,这可能有助于识别可作为生物标志物、可治疗靶点,甚至是改变疾病的药物(OA 药物)的蓝图的分子。在这篇叙述性综述中,我们在 PubMed 上搜索了英文相关文献,并总结了目前关于软骨和 OA 中选定 ECM 分子及其衍生基质细胞因子功能的知识。