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Highly Accessed Review

Transcriptional regulation of collagenase (MMP-1, MMP-13) genes in arthritis: integration of complex signaling pathways for the recruitment of gene-specific transcription factors

Matthew P Vincenti1* and Constance E Brinckerhoff12

Author Affiliations

1 Department of Medicine, Dartmouth Medical School, Hanover, New Hampshire, USA

2 Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire, USA

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Arthritis Res 2002, 4:157-164  doi:10.1186/ar401

Published: 23 November 2001

Abstract

Matrix metalloproteinase (MMP)-1, MMP-8 and MMP-13 are interstitial collagenases that degrade type II collagen in cartilage; this is a committed step in the progression of rheumatoid arthritis and osteoarthritis. Of these enzymes, the expression of MMP-1 and MMP-13 is substantially increased in response to IL-1 and tumor necrosis factor-α, and elevated levels of these collagenases are observed in arthritic tissues. Therefore, cytokine-mediated MMP-1 and MMP-13 gene regulation is an important issue in arthritis research. In this review, we discuss current models of MMP-1 and MMP-13 transcriptional regulation, with a focus on signaling intermediates and transcription factors that may be future targets for the development of new arthritis drugs.

Keywords:
arthritis; matrix metalloproteinases; mitogen-activated protein kinases; nuclear factor κB; transcription