Fibroblast activation protein alpha is expressed by chondrocytes following a pro-inflammatory stimulus and is elevated in osteoarthritis.
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 le...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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BioMed Central
2006
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| _version_ | 1797069240218419200 |
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| author | Milner, J Kevorkian, L Young, D Jones, D Wait, R Donell, S Barksby, E Patterson, A Middleton, J Cravatt, B Clark, I Rowan, A Cawston, T |
| author_facet | Milner, J Kevorkian, L Young, D Jones, D Wait, R Donell, S Barksby, E Patterson, A Middleton, J Cravatt, B Clark, I Rowan, A Cawston, T |
| author_sort | Milner, J |
| collection | OXFORD |
| description | 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 (FAPalpha), a type II integral membrane serine proteinase, was identified on chondrocyte membranes stimulated with IL-1 and OSM. Real-time PCR analysis shows that FAPalpha gene expression is up-regulated 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 FAPalpha expression on chondrocytes in the superficial zone of OA cartilage tissues. This is the first report demonstrating the expression of active FAPalpha 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. |
| first_indexed | 2024-03-06T22:21:32Z |
| format | Journal article |
| id | oxford-uuid:55382c11-b6ca-4ec5-8e63-c04759a439c7 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:21:32Z |
| publishDate | 2006 |
| publisher | BioMed Central |
| record_format | dspace |
| spelling | oxford-uuid:55382c11-b6ca-4ec5-8e63-c04759a439c72022-03-26T16:42:39ZFibroblast activation protein alpha is expressed by chondrocytes following a pro-inflammatory stimulus and is elevated in osteoarthritis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:55382c11-b6ca-4ec5-8e63-c04759a439c7EnglishSymplectic Elements at OxfordBioMed Central2006Milner, JKevorkian, LYoung, DJones, DWait, RDonell, SBarksby, EPatterson, AMiddleton, JCravatt, BClark, IRowan, ACawston, TArthritis 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 (FAPalpha), a type II integral membrane serine proteinase, was identified on chondrocyte membranes stimulated with IL-1 and OSM. Real-time PCR analysis shows that FAPalpha gene expression is up-regulated 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 FAPalpha expression on chondrocytes in the superficial zone of OA cartilage tissues. This is the first report demonstrating the expression of active FAPalpha 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. |
| spellingShingle | Milner, J Kevorkian, L Young, D Jones, D Wait, R Donell, S Barksby, E Patterson, A Middleton, J Cravatt, B Clark, I Rowan, A Cawston, T Fibroblast activation protein alpha is expressed by chondrocytes following a pro-inflammatory stimulus and is elevated in osteoarthritis. |
| title | Fibroblast activation protein alpha is expressed by chondrocytes following a pro-inflammatory stimulus and is elevated in osteoarthritis. |
| title_full | Fibroblast activation protein alpha is expressed by chondrocytes following a pro-inflammatory stimulus and is elevated in osteoarthritis. |
| title_fullStr | Fibroblast activation protein alpha is expressed by chondrocytes following a pro-inflammatory stimulus and is elevated in osteoarthritis. |
| title_full_unstemmed | Fibroblast activation protein alpha is expressed by chondrocytes following a pro-inflammatory stimulus and is elevated in osteoarthritis. |
| title_short | Fibroblast activation protein alpha is expressed by chondrocytes following a pro-inflammatory stimulus and is elevated in osteoarthritis. |
| title_sort | fibroblast activation protein alpha is expressed by chondrocytes following a pro inflammatory stimulus and is elevated in osteoarthritis |
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