Proteases Involved in Cartilage Matrix Degradation in Osteoarthritis

Biochim Biophys Acta. 2012 Jan;1824(1):133-45. doi: 10.1016/j.bbapap.2011.06.020. Epub 2011 Jul 8.

Abstract

Osteoarthritis is a common joint disease for which there are currently no disease-modifying drugs available. Degradation of the cartilage extracellular matrix is a central feature of the disease and is widely thought to be mediated by proteinases that degrade structural components of the matrix, primarily aggrecan and collagen. Studies on transgenic mice have confirmed the central role of Adamalysin with Thrombospondin Motifs 5 (ADAMTS-5) in aggrecan degradation, and the collagenolytic matrix metalloproteinase MMP-13 in collagen degradation. This review discusses recent advances in current understanding of the mechanisms regulating expression of these key enzymes, as well as reviewing the roles of other proteinases in cartilage destruction. This article is part of a Special Issue entitled: Proteolysis 50 years after the discovery of lysosome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ADAM Proteins / genetics
  • ADAM Proteins / metabolism
  • Animals
  • Cartilage / metabolism*
  • Cartilage / pathology
  • Collagenases / genetics
  • Collagenases / metabolism
  • Extracellular Matrix / metabolism*
  • Extracellular Matrix / pathology
  • Gene Expression Regulation, Enzymologic / physiology
  • Humans
  • Matrix Metalloproteinases / genetics
  • Matrix Metalloproteinases / metabolism
  • Mice
  • Models, Biological
  • Osteoarthritis / enzymology
  • Osteoarthritis / genetics
  • Osteoarthritis / metabolism*
  • Osteoarthritis / pathology
  • Peptide Hydrolases / genetics
  • Peptide Hydrolases / metabolism
  • Peptide Hydrolases / physiology*
  • Proteolysis*

Substances

  • Peptide Hydrolases
  • ADAM Proteins
  • Collagenases
  • Matrix Metalloproteinases