Chondroprotective drugs in degenerative joint diseases

Rheumatology (Oxford). 2006 Feb;45(2):129-38. doi: 10.1093/rheumatology/kei171. Epub 2005 Nov 8.


Catabolic cytokine and anabolic growth factor pathways control destruction and repair in osteoarthritis (OA). A unidirectional TNF-alpha/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-alpha 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-alpha-blocking agents that repressed the unidirectional TNF-alpha/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 E(2), 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.

Publication types

  • Review

MeSH terms

  • Antirheumatic Agents / therapeutic use*
  • Cartilage, Articular / drug effects*
  • Cartilage, Articular / physiopathology
  • Cytokines / physiology
  • Growth Substances / physiology
  • Humans
  • Osteoarthritis / drug therapy*
  • Osteoarthritis / physiopathology
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors


  • Antirheumatic Agents
  • Cytokines
  • Growth Substances
  • Tumor Necrosis Factor-alpha