Lafeber F P J G, Miossec P, Valentino L A
Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
Haemophilia. 2008 Jul;14 Suppl 4:3-9. doi: 10.1111/j.1365-2516.2008.01732.x.
Haemophilic arthropathy, which shares some clinical and biological injury characteristics with rheumatoid arthritis, is characterized by two main features: chronic proliferative synovitis and cartilage destruction. It is the consequence of repeated extravasation of blood into joint cavities, but its exact pathogenesis, particularly with regard to early changes in the joint, is still incompletely understood. This review presents recent findings obtained in experiments performed in vitro and using animal models, which have improved our knowledge of the pathogenesis of haemophilic arthropathy. These experimental studies show that haemophilic arthropathy is a multifactorial event in which the deposit of iron in the joints appears to exert a central role. First, iron may promote the apoptosis of chondrocytes by catalysing the formation of oxygen metabolites; this may explain the fact that intra-articular blood exerts a directly harmful effect on cartilage before, and independent of synovial changes. Secondly, iron may also act on the synovial membrane by favouring its proliferation through the induction of proto-oncogenes involved in cellular proliferation and stimulation of inflammatory cytokines as well as abrogation of apoptosis. These two processes, one degenerative and cartilage-mediated, the other inflammatory and synovium-mediated could occur in parallel or sequentially. Overall, it may be expected that these experimental results will yield new therapeutic strategies capable of effectively preventing the occurrence of this still serious and common complication in patients with severe haemophilia.
血友病性关节病与类风湿性关节炎具有一些临床和生物学损伤特征，其主要有两个特点：慢性增殖性滑膜炎和软骨破坏。它是血液反复渗入关节腔的结果，但其确切发病机制，尤其是关节早期变化方面，仍未完全明了。本综述介绍了在体外实验和动物模型实验中获得的最新发现，这些发现增进了我们对血友病性关节病发病机制的认识。这些实验研究表明，血友病性关节病是一个多因素事件，其中关节内铁沉积似乎起核心作用。首先，铁可通过催化氧代谢产物的形成促进软骨细胞凋亡；这或许可以解释关节内血液在滑膜变化之前且独立于滑膜变化对软骨产生直接有害作用这一事实。其次，铁还可通过诱导参与细胞增殖的原癌基因、刺激炎性细胞因子以及抑制细胞凋亡来促进滑膜增殖，从而作用于滑膜。这两个过程，一个是退行性且由软骨介导，另一个是炎症性且由滑膜介导，可能并行或相继发生。总体而言，可以预期这些实验结果将产生新的治疗策略，能够有效预防重度血友病患者中这种仍然严重且常见的并发症的发生。
