Elevation of activated protein C in synovial joints in rheumatoid arthritis and its correlation with matrix metalloproteinase 2

Arthritis and Rheumatism
Nathalie Buisson-LegendreChristopher Jackson

Abstract

To investigate the involvement of the anticoagulant serine protease activated protein C (APC) in tissue remodeling in rheumatoid arthritis (RA). PC/APC, matrix metalloproteinase 2 (MMP-2), and MMP-9 were detected in synovial fluid by Western blotting, and their antigen levels were quantified by enzyme-linked immunosorbent assay in patients with osteoarthritis (OA) or RA. Enzymatic activity of MMP-2 was assayed using a specific fluorogenic substrate. We developed an improved assay to measure APC activity in synovial fluid utilizing a chromogenic substrate following immunoprecipitation with a specific PC/APC antibody. PC/APC and MMP-2 were localized by immunohistochemistry in RA, OA, and normal synovial tissues. Synovial fluid analysis demonstrated that APC is present in both RA and OA synovial fluid, with APC activity being markedly higher in RA (mean +/- SEM 462 +/- 112 ng/ml versus 136 +/- 42 ng/ml; P < 0.02). A correlation (r(2) = 0.61) was found between APC and MMP-2 activity levels in RA patients, but not in OA patients. Immunohistochemical studies of synovial sections showed colocalization of APC and MMP-2 in endothelial and synovial lining cells. Additionally, APC and MMP-2 coimmunoprecipitated with an anti-PC/APC antibod...Continue Reading

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Citations

Aug 2, 2011·Seminars in Immunopathology·Edward M Conway
Sep 29, 2007·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Anthony L NewsomeMichael W Thompson
Aug 18, 2012·Advances in Orthopedics·Olimpio GalassoGiorgio Gasparini
Jul 11, 2008·Expert Opinion on Biological Therapy·Chris JacksonMeilang Xue
Oct 4, 2012·Topics in Companion Animal Medicine·Amy Kubier, Mauria O'Brien
Feb 6, 2008·The International Journal of Biochemistry & Cell Biology·Christopher J Jackson, Meilang Xue
Feb 28, 2009·Arthritis and Rheumatism·Miriam T JacksonChristopher B Little
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Sep 25, 2009·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Elaine R GarvicanPeter D Clegg
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Dec 28, 2019·Cells·Selene Pérez-GarcíaRosa P Gomariz
Mar 3, 2020·Frontiers in Physiology·Eugenio Hardy, Carlos Fernandez-Patron

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