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

Arthritis Res. 2002;4(3):157-64. doi: 10.1186/ar401. Epub 2001 Nov 23.

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-alpha, 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Arthritis, Rheumatoid / enzymology*
  • Arthritis, Rheumatoid / genetics
  • Collagenases / genetics*
  • Gene Expression Regulation, Enzymologic*
  • Humans
  • Matrix Metalloproteinase 1 / genetics*
  • Matrix Metalloproteinase 13
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • NF-kappa B / metabolism
  • Osteoarthritis / enzymology*
  • Osteoarthritis / genetics
  • Signal Transduction
  • Transcription Factors / physiology*

Substances

  • NF-kappa B
  • Transcription Factors
  • Mitogen-Activated Protein Kinase Kinases
  • Collagenases
  • MMP13 protein, human
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinase 1