title: Fibroblast activation protein is expressed by rheumatoid myofibroblast-like synoviocytes.
abstract: Fibroblast activation protein (FAP), as described so far, is a type II cell surface serine protease expressed by fibroblastic cells in areas of active tissue remodelling such as tumour stroma or healing wounds. We investigated the expression of FAP by fibroblast-like synoviocytes (FLSs) and compared the synovial expression pattern in rheumatoid arthritis (RA) and osteoarthritis (OA) patients. Synovial tissue from diseased joints of 20 patients, 10 patients with refractory RA and 10 patients with end-stage OA, was collected during routine surgery. As a result, FLSs from intensively inflamed synovial tissues of refractory RA expressed FAP at high density. Moreover, FAP expression was co-localised with matrix metalloproteinases (MMP-1 and MMP-13) and CD44 splice variants v3 and v7/8 known to play a major role in the concert of extracellular matrix degradation. The pattern of signals appeared to constitute a characteristic feature of FLSs involved in rheumatoid arthritic joint-destructive processes. These FAP-expressing FLSs with a phenotype of smooth muscle actin-positive myofibroblasts were located in the lining layer of the synovium and differ distinctly from Thy-1-expressing and non-proliferating fibroblasts of the articular matrix. The intensity of FAP-specific staining in synovial tissue from patients with RA was found to be different when compared with end-stage OA. Because expression of FAP by RA FLSs has not been described before, the findings of this study highlight a novel element in cartilage and bone destruction of arthritic joints. Moreover, the specific expression pattern qualifies FAP as a therapeutic target for inhibiting the destructive potential of fibroblast-like synovial cells.
authors.affiliation: Oncology Department, UniversitätsSpital Zürich, Rämistrasse 100, 8091 Zürich, Switzerland. stefan.bauer@usz.ch
authors.forename: Stefan
authors.initials: S
authors.lastname: Bauer
authors.forename: Michael C
authors.initials: MC
authors.lastname: Jendro
authors.forename: Andreas
authors.initials: A
authors.lastname: Wadle
authors.forename: Sascha
authors.initials: S
authors.lastname: Kleber
authors.forename: Frank
authors.initials: F
authors.lastname: Stenner
authors.forename: Robert
authors.initials: R
authors.lastname: Dinser
authors.forename: Anja
authors.initials: A
authors.lastname: Reich
authors.forename: Erica
authors.initials: E
authors.lastname: Faccin
authors.forename: Stefan
authors.initials: S
authors.lastname: Gödde
authors.forename: Harald
authors.initials: H
authors.lastname: Dinges
authors.forename: Ulf
authors.initials: U
authors.lastname: Müller-Ladner
authors.forename: Christoph
authors.initials: C
authors.lastname: Renner
mesh_terms: D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D010450:Endopeptidases; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D018093:Gelatinases; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D008565:Membrane Proteins; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D010003:Osteoarthritis / Q000378:metabolism; D010641:Phenotype; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000096:biosynthesis*; D013583:Synovial Membrane / Q000166:cytology* / Q000378:metabolism* / Q000473:pathology; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D010450:Endopeptidases; D018093:Gelatinases; D018960:Hyaluronan Receptors; D020781:Matrix Metalloproteinase 1; D053509:Matrix Metalloproteinase 13; D008565:Membrane Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha