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Contribution of Reactive Oxygen Species to Cartilage Degradation in Rheumatic Diseases: Molecular Pathways, Diagnosis and Potential Therapeutic Strategies

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Abstract:

Inflammatory joint diseases are of considerable socio-economic significance. However, mechanisms of cartilage destruction are so far only poorly understood. This review is dedicated to reactive oxygen species (ROS) like superoxide anion radicals, hydrogen peroxide, singlet oxygen, hypochlorous acid, hydroxyl radicals and nitric oxide that are generated under inflammatory conditions and also to their potential contribution to cartilage degradation.

First, the relevance of rheumatic diseases and potential mechanisms of cartilage degradation are discussed in this review, followed by the description of the chemical constituents and the molecular architecture of articular cartilage as well as the different cell types that play a role in inflammation and cartilage destruction. Methods of the assessment of cartilage degeneration are also shortly discussed.

In the main chapter of this review the characteristics of individual ROS, their generation under in vivo conditions as well as their reactivities with individual cartilage components are discussed. Because of the low selectivity of ROS, useful “markers” of cartilage degradation allowing the differentiation of effects induced by individual ROS are also discussed.

In the last chapter current therapeutic concepts of the treatment of rheumatic diseases are reviewed. The recently developed “anti-TNF-α” therapy that is primarily directed against neutrophilic granulocytes that are powerful sources of ROS and, therefore, important mediators of joint degeneration are emphasised.

Keywords: arthritis; cartilage; inflammation; neutrophils; reactive oxygen species; synovia

Document Type: Review Article

DOI: http://dx.doi.org/10.2174/0929867033456828

Affiliations: Institut fur Medizinische Physik und Biophysik, Universitat Leipzig, Medizinische Fakultat, Liebigstr. 27, D-04103 Leipzig, Germany

Publication date: October 1, 2003

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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