Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, Canada.
Adv Clin Chem. 2021;101:95-120. doi: 10.1016/bs.acc.2020.06.001. Epub 2020 Jul 7.
Osteoarthritis (OA) is a multifactorial disease with huge phenotypic heterogeneity. The disease affects all tissues in the joint, and the loss of articular cartilage is its hallmark. The main biochemical components of the articular cartilage are type II collagen, aggrecan, and water. Transforming growth factor-beta (TGF-β) signaling is one of the signaling pathways that maintains the healthy cartilage. However, the two subpathways of the TGF-β signaling-TGF-β and bone morphogenetic proteins (BMP) subpathways, lose their balance in OA, resulting an increased expression of cartilage degradation enzymes including matrix metallopeptidase 13 (MMP13), cathepsin B (CTSB), and cathepsin K (CTSK) and a decreased expression of aggrecan (ACAN). Thus, restoring the balance of two subpathways might provide a new avenue for treating OA patients. Further, metabolic changes are seen in OA and can be used to distinguish different subtypes of OA patients. Metabolomics studies showed that at least three endotypes of OA can be distinguished: 11% of OA patients are characterized by an elevated blood butyryl carnitine, 33% of OA patients have significant reduced arginine concentration, and 56% with metabolic alteration in phospholipid metabolism. While these findings need to be confirmed, they are promising personalized medicine tools for OA management.
骨关节炎（OA）是一种多因素疾病，具有巨大的表型异质性。该疾病影响关节的所有组织，其标志性特征是关节软骨的丧失。关节软骨的主要生化成分包括 II 型胶原、聚集蛋白聚糖和水。转化生长因子-β（TGF-β）信号是维持健康软骨的信号通路之一。然而，TGF-β 信号的两个亚通路——TGF-β和骨形态发生蛋白（BMP）亚通路，在 OA 中失去平衡，导致软骨降解酶如基质金属蛋白酶 13（MMP13）、组织蛋白酶 B（CTSB）和组织蛋白酶 K（CTSK）的表达增加，聚集蛋白聚糖（ACAN）的表达减少。因此，恢复两个亚通路的平衡可能为治疗 OA 患者提供新的途径。此外，OA 中存在代谢变化，可以用于区分不同亚型的 OA 患者。代谢组学研究表明，至少可以区分三种 OA 表型：11%的 OA 患者的血液丁酰肉碱水平升高，33%的 OA 患者的精氨酸浓度显著降低，56%的 OA 患者的磷脂代谢发生代谢改变。虽然这些发现需要进一步证实，但它们是 OA 管理有前景的个性化医学工具。
