Rheumatology Advance Access originally published online on November 8, 2005
Rheumatology 2006 45(2):129-138; doi:10.1093/rheumatology/kei171
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Chondroprotective drugs in degenerative joint diseases
Department of Rheumatology, Ghent University Hospital, Ghent University, Ghent, Belgium.
Correspondence to: G. Verbruggen, Polikliniek Reumatologie, 0K12, Universitair Hospitaal, De Pintelaan 185, B-9000 Ghent, Belgium. E-mail: gust.verbruggen{at}ugent.be
Catabolic cytokine and anabolic growth factor pathways control destruction and repair in osteoarthritis (OA). A unidirectional TNF-
/IL-1-driven cytokine cascade disturbs the homeostasis of the extracellular matrix of articular cartilage in OA. Although chondrocytes in OA cartilage overexpress anabolic insulin-like growth factor (IGF) and its specific receptor (IGFRI) autocrine TNF- released by apoptotic articular cartilage cells sets off an auto/paracrine IL-1-driven cascade that overrules the growth factor activities that sustain repair in degenerative joint disease. Chondroprotection with reappearance of a joint space that had disappeared has been documented unmistakably in peripheral joints of patients suffering from spondyloarthropathy when treated with TNF--blocking agents that repressed the unidirectional TNF-/IL-1-driven cytokine cascade. A series of connective tissue structure-modifying agents (CTSMAs) that directly affect IL-1 synthesis and release in vitro and down-modulate downstream IL-1 features, e.g. collagenase, proteoglycanase and matrix metalloproteinase activities, the expression of inducible nitric oxide synthase, the increased release of nitric oxide, and the secretion of prostaglandin E2, IL-6 and IL-8, have been shown to possess disease-modifying OA drug (DMOAD) activities in experimental models of OA and in human subjects with finger joint and knee OA. Examples are corticosteroids, some sulphated polysaccharides, chemically modified tetracyclines, diacetylrhein/rhein, glucosamine and avocado/soybean unsaponifiables.
KEY WORDS: Osteoarthritis, TNF-, IL-1, Chondroprotection, DMOADs
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