Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

The role of human HtrA1 in arthritic disease

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

Full text not available from this repository.


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
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: 24 Oct 2022 10:13

Citation Data

Cited 230 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item