Collagenase gene regulation by pro-inflammatory cytokines in cartilage.
The essentially irreversible degradation of articular cartilage collagen represents a key, rate-limiting process in arthritic diseases. This process is typically initiated as a consequence of an inflammatory response, and if left unchecked ultimately leads to loss of joint function, pain, disability and a need for joint replacement surgery. Although we have identified the enzymes capable of effecting such destructive proteolysis, and considerable evidence indicates that tumour necrosis factor alpha and interleukin-1 are major pro-inflammatory mediators in joint destruction, we still know relatively little about how these mediators regulate collagenase gene expression in chondrocytes. Inflammatory arthritis has long been considered to be synovium-driven but compelling data now also implicate the chondrocyte, the sole cell type present in cartilage, as an active player in the destructive process. An understanding of how different cytokines interact, and how the pathways they activate cross-talk will not only provide important new insight into the mechanisms of joint destruction but also identify new targets for therapeutic intervention.
Rowan
Andrew D
AD
Musculoskeletal Research Group, School of Clinical Medical Sciences, Catherine Cookson Building, Medical School, Framlington Place, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, United Kingdom. a.d.rowan@ncl.ac.uk
Young
David A
DA
D000818:Animals; D002356:Cartilage / Q000201:enzymology* / Q000502:physiology; D019902:Chondrocytes / Q000201:enzymology; D017364:Collagenases / Q000235:genetics* / Q000378:metabolism; D016207:Cytokines / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology; D053505:Matrix Metalloproteinases, Secreted / Q000235:genetics* / Q000378:metabolism
D016207:Cytokines; D018836:Inflammation Mediators; D017364:Collagenases; D053505:Matrix Metalloproteinases, Secreted