title: Fibroblast activation protein alpha is expressed by chondrocytes following a pro-inflammatory stimulus and is elevated in osteoarthritis.
abstract: 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.
authors.affiliation: Musculoskeletal Research Group, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Milner
authors.forename: Lara
authors.initials: L
authors.lastname: Kevorkian
authors.forename: David A
authors.initials: DA
authors.lastname: Young
authors.forename: Debra
authors.initials: D
authors.lastname: Jones
authors.forename: Robin
authors.initials: R
authors.lastname: Wait
authors.forename: Simon T
authors.initials: ST
authors.lastname: Donell
authors.forename: Emma
authors.initials: E
authors.lastname: Barksby
authors.forename: Angela M
authors.initials: AM
authors.lastname: Patterson
authors.forename: Jim
authors.initials: J
authors.lastname: Middleton
authors.forename: Benjamin F
authors.initials: BF
authors.lastname: Cravatt
authors.forename: Ian M
authors.initials: IM
authors.lastname: Clark
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Rowan
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Cawston
mesh_terms: D000818:Animals; D002356:Cartilage / Q000378:metabolism; D002358:Cartilage, Articular / Q000378:metabolism; D002417:Cattle; D002462:Cell Membrane / Q000737:chemistry; D002478:Cells, Cultured; D019902:Chondrocytes / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D016207:Cytokines / Q000494:pharmacology*; D010450:Endopeptidases; D018093:Gelatinases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000494:pharmacology*; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D053683:Oncostatin M; D010003:Osteoarthritis / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D046509:Tissue Culture Techniques; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D016207:Cytokines; D010450:Endopeptidases; D018093:Gelatinases; D007375:Interleukin-1; D008565:Membrane Proteins; D053683:Oncostatin M; D011994:Recombinant Proteins; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha; C508351:OSM protein, human