کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3367385 1218438 2006 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Cartilage breakdown in rheumatoid arthritis
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی ایمونولوژی، آلرژی و روماتولوژی
پیش نمایش صفحه اول مقاله
Cartilage breakdown in rheumatoid arthritis
چکیده انگلیسی

Rheumatoid arthritis (RA) is a connective tissue disease characterized by destruction of the joint cartilage and subsequently of the underlying bone. Cartilage destruction is due to proteolysis by enzymes called metalloproteinases (MMPs), whose production and expression are regulated by numerous local mediators such as cytokines, growth factors, prostaglandins, oxygen species, and neuropeptides. MMP activation is largely due to a stimulatory effect of cytokines including IL-1β and TNFα. When these cytokines bind to their membrane receptor, they set off signaling cascades, with activation of TGFβ-activating kinase (TAK-1), of NF-κB by Iκ-B kinase, of mitogen-activated protein kinases (MAP kinases), and finally of activator protein-1 (AP-1). Tissue inhibitors of MMPs (TIMPs) specifically inhibit MMPs. The interrelations between joint inflammation and joint destruction remain poorly understood. Experimental data suggest that IL-1 may be involved chiefly in joint destruction and TNF in joint inflammation. However, TNF antagonists are potent inhibitors of joint destruction in clinical practice. These results suggest that the mediators function as a network and that inhibition of a single mediator can affect the entire web. Insights gained into the innermost mechanisms of cartilage breakdown in patients with RA have led to major therapeutic breakthroughs. Thus, TNF antagonists have proved highly effective in RA. Future progress will no doubt stem from new knowledge about the extracellular mediators and intracellular signaling pathways that lead to the production and activation of enzymes responsible for cartilage degradation.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Joint Bone Spine - Volume 73, Issue 1, January 2006, Pages 29–36
نویسندگان
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