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Lookup NU author(s): Dr Jenny Milner, Professor David YoungORCiD, David Jones, Dr Emma Barksby, Dr Angela Patterson, Emeritus Professor Drew Rowan, Emeritus Professor Tim Cawston
Arthritis is characterised by the proteolytic degradation of articular cartilage leading to a loss of joint function. Articular cartilage is composed of an extracellular matrix of proteoglycans and collagens. We have previously shown that serine proteinases are involved in the activation cascades leading to cartilage collagen degradation. The aim of this study was to use an active-site probe, biotinylated fluorophosphonate, to identify active serine proteinases present on the chondrocyte membrane after stimulation with the pro-inflammatory cytokines IL-1 and oncostatin M (OSM), agents that promote cartilage resorption. Fibroblast activation protein alpha (FAP alpha), a type II integral membrane serine proteinase, was identified on chondrocyte membranes stimulated with IL-1 and OSM. Realtime PCR analysis shows that FAP alpha gene expression is upregulated by this cytokine combination in both isolated chondrocytes and cartilage explant cultures and is significantly higher in cartilage from OA patients compared to phenotypically normal articular cartilage. Immunohistochemistry analysis shows FAPa expression on chondrocytes in the superficial zone of OA cartilage tissues. This is the first report demonstrating the expression of active FAPa on the chondrocyte membrane and elevated levels in cartilage from OA patients. Its cell surface location and expression profile suggest that it may have an important pathological role in the cartilage turnover prevalent in arthritic diseases.
Author(s): Milner JM, Kevorkian L, Young DA, Jones D, Wait R, Donell ST, Barksby HE, Patterson AM, Middleton JM, Cravatt BF, Clark IM, Rowan AD, Cawston TE
Publication type: Article
Publication status: Published
Journal: Arthritis Research & Therapy
Year: 2006
Volume: 8
Issue: 1
ISSN (print): 1478-6354
ISSN (electronic): 1478-6362
Publisher: BioMed Central Ltd.
URL: http://dx.doi.org/10.1186/ar1877
DOI: 10.1186/ar1877
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