Articular cartilage destruction in experimental inflammatory arthritis: insulin-like growth factor-1 regulation of proteoglycan metabolism in chondrocytes.
Rheumatoid arthritis, a disease of unknown aetiology, is characterized by joint inflammation and, in its later stages, cartilage destruction. Inflammatory mediators may exert not only suppression of matrix synthesis but also cartilage degradation, which eventually leads to severe cartilage depletion. Systemically and locally produced growth factors and hormones regulate cartilage metabolism. Alterations in levels of these factors or in their activity can influence the pathogenesis of articular cartilage destruction in arthritic joints. The main topic of the present review is the role of the anabolic factor insulin-like growth factor-1 in the regulation of chondrocyte metabolic functions in normal and in diseased cartilage. This is the most important growth factor that balances chondrocytes proteoglycan synthesis and catabolism to maintain a functional cartilage matrix. A brief overview of how chondrocytes keep the cartilage matrix intact, and how catabolic and anabolic factors are thought to be involved in pathological cartilage destruction precedes the review of the role of this growth factor in proteoglycan metabolism in cartilage.
Verschure
P J
PJ
Department of Rheumatology, University Hospital Nijmegen, The Netherlands.
Van Noorden
C J
CJ
Van Marle
J
J
Van den Berg
W B
WB
D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000473:pathology*; D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D010450:Endopeptidases / Q000378:metabolism; D005938:Glucocorticoids / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D018613:Microscopy, Confocal; D010100:Oxygen / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism*
D005938:Glucocorticoids; D006133:Growth Substances; D018969:Insulin-Like Growth Factor Binding Proteins; D011509:Proteoglycans; D007334:Insulin-Like Growth Factor I; D010450:Endopeptidases; D010100:Oxygen