Korb Adelheid, Pavenstädt Hermann, Pap Thomas
Department of Internal Medicine, University Hospital Muenster, Munster, Germany.
Apoptosis. 2009 Apr;14(4):447-54. doi: 10.1007/s10495-009-0317-y.
Apoptosis plays a pivotal role in tissue homoeostasis both under physiological and pathological conditions and several studies have shown that some characteristic changes in the composition and structure of the inflamed synovial membrane in rheumatoid arthritis (RA) are linked to an altered apoptotic response of synovial cells. As a result, a hyperplastic synovial tissue is generated that mediates the progressive destruction of articular cartilage and bone. In addition to inflammatory cells, these changes most prominently affect resident fibroblast-like cells that have been demonstrated to be of utmost importance for joint destruction. Once activated, these cells pass through prominent molecular changes resulting in an aggressive, invasive behaviour. Research of the past years has identified different mechanisms that prevent synovial cells in RA from apoptosis. They include changes in the mitochondrial pathway as well as altered expression of downstream modulators of death receptors and transcriptional regulators such as NFkappaB. This review summarises our recent progress in understanding aberrant apoptosis in the RA synovial membrane and points to possibilities of intervening specifically with this aspect of the pathogenesis of RA.
细胞凋亡在生理和病理条件下的组织稳态中都起着关键作用，多项研究表明，类风湿关节炎（RA）中炎症滑膜的组成和结构的一些特征性变化与滑膜细胞凋亡反应的改变有关。结果，产生了增生性滑膜组织，介导关节软骨和骨的渐进性破坏。除炎症细胞外，这些变化最显著地影响驻留的成纤维样细胞，已证明这些细胞对关节破坏至关重要。一旦被激活，这些细胞会经历显著的分子变化，导致侵袭性、侵入性行为。过去几年的研究已经确定了不同的机制来阻止RA中的滑膜细胞凋亡。它们包括线粒体途径的变化以及死亡受体下游调节因子和转录调节因子（如核因子κB）表达的改变。本综述总结了我们在理解RA滑膜异常细胞凋亡方面的最新进展，并指出了特异性干预RA发病机制这一方面的可能性。
