Molecular aspects of pathogenesis in osteoarthritis: the role of inflammation.
Arthritic diseases cause enormous burdens in terms of pain, crippling, and disability. Osteoarthritis (OA), the most common form of arthritis, is characterized by a slow progressive degeneration of articular cartilage. The exact etiology of OA is not known, but the degradation of cartilage matrix components is generally agreed to be due to an increased synthesis and activation of extracellular proteinases, mainly matrix metalloproteinases. Insufficient synthesis of new matrix macromolecules is also thought to be involved, possibly as a consequence of deficient stimulation by growth factors. Although OA is defined as a noninflammatory arthropathy, proinflammatory cytokines such as interleukin-1 have been implicated as important mediators in the disease. In response to interleukin-1, chondrocytes upregulate the production of nitric oxide and prostaglandin E2, two factors that have been shown to induce a number of the cellular changes associated with OA. The generation of these key signal molecules depends on inducible enzymes and can be suppressed by pharmacological inhibitors.
Hedbom
E
E
Laboratory for Experimental Cartilage Research, Center for Rheumatology and Bone Disease, Zürich, Switzerland. ehedbom@rheumazentrum.ch
Häuselmann
H J
HJ
D051722:ADAM Proteins; D000071121:ADAMTS4 Protein; D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D019902:Chondrocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008666:Metalloendopeptidases / Q000378:metabolism; D010003:Osteoarthritis / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D011348:Procollagen N-Endopeptidase
D016207:Cytokines; D051722:ADAM Proteins; D020782:Matrix Metalloproteinases; D008666:Metalloendopeptidases; D011348:Procollagen N-Endopeptidase; D000071121:ADAMTS4 Protein