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The role of human HtrA1 in arthritic disease

Grau, Sandra, Richards, Peter J., Kerr, Briedgeen, Hughes, Clare Elizabeth, Caterson, Bruce, Williams, Anwen Sian, Junker, Uwe, Jones, Simon Arnett, Clausen, Tim and Ehrmann, Michael 2006. The role of human HtrA1 in arthritic disease. The Journal of Biological Chemistry 281 (10) , pp. 6124-6129. 10.1074/jbc.M500361200

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Abstract

Human HtrA1 belongs to a widely conserved family of serine proteases involved in various aspects of protein quality control and cell fate. Although HtrA1 has been implicated in the pathology of several diseases, its precise biological functions remain to be established. Through identification of potential HtrA1 targets, studies presented herein propose that within the context of arthritis pathology HtrA1 contributes to cartilage degradation. Elevated synovial HtrA1 levels were detected in fluids obtained from rheumatoid and osteoarthritis patients, with synovial fibroblasts identified as a major source of secreted HtrA1. Mass spectrometry analysis of potential HtrA1 substrates within synovial fluids identified fibronectin as a candidate target, and treatment of fibronectin with recombinant HtrA1 led to the generation of fibronectin-degradation products that may be involved in cartilage catabolism. Consistently, treatment of synovial fibroblasts with HtrA1 or HtrA1-generated fibronectin fragments resulted in the specific induction of matrix metalloprotease 1 and matrix metalloprotease 3 expression, suggesting that HtrA1 contributes to the destruction of extracellular matrix through both direct and indirect mechanisms.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Medicine
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QH Natural history > QH426 Genetics
Q Science > QR Microbiology > QR180 Immunology
R Medicine > RC Internal medicine
Publisher: American Society for Biochemistry and Molecular Biology
ISSN: 0021-9258
Last Modified: 13 Aug 2018 20:32
URI: http://orca.cf.ac.uk/id/eprint/43467

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