Department of Rheumatology, Radboud University, Medical Centre, Geert Grooteplein 28, 6525 Nijmegen, The Netherlands.
Osteoarthritis Cartilage. 2012 Mar;20(3):223-32. doi: 10.1016/j.joca.2011.12.003. Epub 2011 Dec 11.
To review the literature on the role and regulation of chondrocyte terminal differentiation (hypertrophy-like changes) in osteoarthritis (OA) and to integrate this in a conceptual model of primary OA development.
Papers investigating chondrocyte terminal differentiation in human OA cartilage and experimental models of OA were recapitulated and discussed. Focus has been on the occurrence of hypertrophy-like changes in chondrocytes and the factors described to play a role in regulation of chondrocyte hypertrophy-like changes in OA.
Chondrocyte hypertrophy-like changes are reported in both human OA and experimental OA models by most investigators. These changes play a crucial part in the OA disease process by protease-mediated cartilage degradation. We propose that altered chondrocyte behavior and concomitant cartilage degradation result in a disease-amplifying loop, leading to a mixture of disease stages and cellular responses within an OA joint.
Chondrocyte hypertrophy-like changes play a role in early and late stage OA. Since not all cells in an OA joint are synchronized, inhibition of hypertrophy-like changes might be a therapeutic target to slow down further OA progression.
回顾关于软骨细胞终末分化(肥大样改变)在骨关节炎(OA)中的作用和调节的文献,并将其整合到原发性 OA 发展的概念模型中。
综述和讨论了研究人 OA 软骨和 OA 实验模型中软骨细胞终末分化的论文。重点关注软骨细胞肥大样改变的发生以及描述的在 OA 中调节软骨细胞肥大样改变的因素。
大多数研究人员在人 OA 和实验性 OA 模型中均报告了软骨细胞肥大样改变。这些变化通过蛋白酶介导的软骨降解在 OA 疾病进程中起着至关重要的作用。我们提出,改变的软骨细胞行为和伴随的软骨降解导致疾病放大循环,导致 OA 关节内出现疾病阶段和细胞反应的混合。
软骨细胞肥大样改变在早期和晚期 OA 中起作用。由于 OA 关节内并非所有细胞都同步,因此抑制肥大样改变可能是减缓 OA 进一步进展的治疗靶点。