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Serine proteinases in the turnover of the cartilage extracellular matrix in the joint: implications for therapeutics.

Authors
  • Wilkinson, David J1
  • Arques, Maria Del Carmen1
  • Huesa, Carmen2
  • Rowan, Andrew D1
  • 1 Skeletal Research Group, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
  • 2 Institute of Biomedical and Environmental Health Research, University of the West of Scotland, Paisley, UK.
Type
Published Article
Journal
British Journal of Pharmacology
Publisher
Wiley (Blackwell Publishing)
Publication Date
Jan 01, 2019
Volume
176
Issue
1
Pages
38–51
Identifiers
DOI: 10.1111/bph.14173
PMID: 29473950
Source
Medline
Language
English
License
Unknown

Abstract

Cartilage destruction is a key characteristic of arthritic disease, a process now widely established to be mediated by metzincins such as MMPs. Despite showing promise in preclinical trials during the 1990s, MMP inhibitors for the blockade of extracellular matrix turnover in the treatment of cancer and arthritis failed clinically, primarily due to poor selectivity for target MMPs. In recent years, roles for serine proteinases in the proteolytic cascades leading to cartilage destruction have become increasingly apparent, renewing interest in the potential for new therapeutic strategies that utilize pharmacological inhibitors against this class of proteinases. Herein, we describe key serine proteinases with likely importance in arthritic disease and highlight recent advances in this field. LINKED ARTICLES: This article is part of a themed section on Translating the Matrix. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.1/issuetoc. © 2018 The British Pharmacological Society.

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