Pathogenesis of bone and cartilage destruction in rheumatoid arthritis

被引:224
作者
Goldring, SR [1 ]
机构
[1] Harvard Univ, Sch Med, New England Baptist Bone & Joint Inst, Boston, MA USA
关键词
bone; cartilage; cytokines; interleukin-1; osteoclast; receptor activator of nuclear factor-kappa B ligand; rheumatoid arthritis; turnour necrosis factor alpha;
D O I
10.1093/rheumatology/keg327
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:11 / 16
页数:6
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