Aigner Thomas, Söder Stefan, Gebhard Pia M, McAlinden Audrey, Haag Jochen
Institute of Pathology, University of Leipzig, Germany.
Nat Clin Pract Rheumatol. 2007 Jul;3(7):391-9. doi: 10.1038/ncprheum0534.
The extracellular matrix of articular cartilage is the primary target of osteoarthritic cartilage degradation. However, cartilage cells have a pivotal role during osteoarthritis, as they are mainly responsible for the anabolic-catabolic balance required for matrix maintenance and tissue function. In addition to the severe changes in the extracellular matrix, the cells also display abnormalities during osteoarthritic cartilage degeneration, such as inappropriate activation of anabolic and catabolic activities, and alterations in cell number through processes like proliferation and (apoptotic) cell death. The cells are exposed to additional stimuli such as nonphysiologic loading conditions and byproducts of matrix destruction, as well as abnormal levels of cytokines and growth factors. This exposure can lead to a structured cellular response pattern that may be either beneficial or detrimental to the cartilage tissue. Potentially even more problematic for preserving tissue homeostasis, neighboring osteoarthritic chondrocytes display strong heterogeneity in their phenotype, gene expression patterns, and cellular responses. As the disease progresses, osteoarthritic chondrocytes can no longer maintain tissue integrity. Evidence suggests that cell aging is important in the pathogenesis of osteoarthritis. Thus, anti-aging strategies might complement existing therapeutic targets related to anabolism, catabolism, inflammation, and apoptosis-processes that are integral to the pathogenesis of osteoarthritis.
关节软骨的细胞外基质是骨关节炎软骨降解的主要靶点。然而，软骨细胞在骨关节炎过程中起着关键作用，因为它们主要负责维持基质和组织功能所需的合成代谢与分解代谢平衡。除了细胞外基质的严重变化外，在骨关节炎软骨退变过程中细胞也会出现异常，如合成代谢和分解代谢活动的不适当激活，以及通过增殖和（凋亡）细胞死亡等过程导致的细胞数量改变。细胞会受到额外的刺激，如非生理负荷条件和基质破坏的副产品，以及细胞因子和生长因子的异常水平。这种暴露可导致一种结构化的细胞反应模式，对软骨组织可能有益也可能有害。对于维持组织稳态而言，潜在问题更大的是，相邻的骨关节炎软骨细胞在其表型、基因表达模式和细胞反应方面表现出强烈的异质性。随着疾病进展，骨关节炎软骨细胞无法再维持组织完整性。有证据表明细胞衰老在骨关节炎发病机制中很重要。因此，抗衰老策略可能会补充现有的与合成代谢、分解代谢、炎症和凋亡相关的治疗靶点，而这些过程是骨关节炎发病机制所不可或缺的。
