Pathogenesis of bone and cartilage destruction in rheumatoid arthritis
Pathogenesis of bone and cartilage destruction in rheumatoid arthritis
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DOI：
10.1093/rheumatology/keg327
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发表时间：
2003-05-01
期刊：
影响因子：
5.5
通讯作者：
Goldring, SR
中科院分区：
文献类型：
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作者：
Goldring, SR
促炎症细胞因子，如白介素1(IL-1)和肿瘤坏死因子α(TNFpha)，被认为与类风湿关节炎(RA)骨和软骨重塑的失调有关。在骨重建方面，这两种细胞因子都被证明上调核因子受体激活物-kappaB配体的产生，从而促进破骨细胞性骨吸收。肿瘤坏死因子α刺激破骨细胞前体细胞分化为成熟的破骨细胞，IL-1直接作用于破骨细胞，增加这些细胞的骨吸收能力。IL-1和TNFpha对软骨重塑也有不利影响，尽管IL-1在摩尔基础上更有效。这种细胞因子不仅增加刺激软骨基质降解的因子的产生，而且还抑制II型胶原和蛋白多糖的合成。加强对关节破坏过程潜在机制的了解，将允许更有选择和更具体地应用针对这些促炎细胞因子的治疗剂，从而更有效地治疗RA和其他炎症性疾病患者。
Proinflammatory cytokines, such as interleukin-1 (IL-1) and tumour necrosis factor alpha (TNFalpha), have been implicated in the dysregulation of bone and cartilage remodelling characteristic of rheumatoid arthritis (RA). With respect to bone remodelling, both of these cytokines have been shown to up-regulate the production of the receptor activator of nuclear factor-kappaB ligand, which acts to enhance osteoclastic bone resorption. TNFalpha stimulates differentiation of osteoclast progenitors into mature osteoclasts and IL-1 acts directly on osteoclasts to increase the bone-resorbing capacity of these cells. IL-1 and TNFalpha also adversely affect cartilage remodelling, although IL-1 is more potent on a molar basis. This cytokine not only increases production of factors that stimulate cartilage matrix degradation, but also inhibits the synthesis of type II collagen and proteoglycans. Enhanced understanding of the mechanisms underlying the processes of joint destruction will allow more selective and specific application of therapeutic agents that target these proinflammatory cytokines and, thus, more effective management of patients with RA and other inflammatory disorders.