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Collagenase gene regulation by pro-inflammatory cytokines in cartilage

Lookup NU author(s): Emeritus Professor Drew Rowan, Professor David YoungORCiD

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Abstract

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.

Publication metadata

Author(s): Rowan AD, Young DA

Publication type: Article

Publication status: Published

Journal: Frontiers in Bioscience

Year: 2007

Volume: 12

Issue: 2

Pages: 536-550

Print publication date: 01/01/2007

ISSN (print): 1093-9946

ISSN (electronic): 1094-3935

Publisher: Frontiers in Bioscience

URL: http://dx.doi.org/10.2741/2080

DOI: 10.2741/2080

PubMed id: 17127315

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