title: The identification and characterization of a novel protein, c19orf10, in the synovium.
abstract: Joint inflammation and destruction have been linked to the deregulation of the highly synthetic fibroblast-like synoviocytes (FLSs), and much of our current understanding of the mechanisms that underlie synovitis has been collected from studies of FLSs. During a proteomic analysis of FLS cells, we identified a novel protein, c19orf10 (chromosome 19 open reading frame 10), that was produced in significant amounts by these cells. The present study provides a partial characterization of c19orf10 in FLSs, synovial fluid, and the synovium. Murine monoclonal and chicken polyclonal antibodies were produced against recombinant human c19orf10 protein and used to examine the distribution of c19orf10 in cultured FLSs and in synovial tissue sections from patients with rheumatoid arthritis or osteoarthritis. The intracellular staining pattern of c19orf10 is consistent with localization in the endoplasmic reticulum/Golgi distribution. Sections of rheumatoid arthritis and osteoarthritis synovia expressed similar patterns of c19orf10 distribution with perivascular and synovial lining staining. Double-staining in situ analysis suggests that fibroblast-like synovial cells produced c19orf10, whereas macrophages, B cells, or T cells produced little or none of this protein. There is evidence of secretion into the vascular space and the extracellular matrix surrounding the synovial lining. A competitive enzyme-linked immunosorbent assay confirmed the presence of microgram levels of c19orf10 in the synovial fluids of patients with one of various arthropathies. Collectively, these results suggest that c19orf10 is an FLS-derived protein that is secreted into the synovial fluid. However, the significance of this protein in synovial biology remains to be determined. The absence of known structural motifs or domains and its relatively late evolutionary appearance raise interesting questions about its function.
authors.affiliation: Department of Internal Medicine and Manitoba Centre for Proteomics and Systems Biology, University of Manitoba, 715 McDermot Avenue, Winnipeg, Manitoba, R3E 3P4, Canada. traceyweiler@gmail.com
authors.forename: Tracey
authors.initials: T
authors.lastname: Weiler
authors.forename: Qiujiang
authors.initials: Q
authors.lastname: Du
authors.forename: Oleg
authors.initials: O
authors.lastname: Krokhin
authors.forename: Werner
authors.initials: W
authors.lastname: Ens
authors.forename: Ken
authors.initials: K
authors.lastname: Standing
authors.forename: Hani
authors.initials: H
authors.lastname: El-Gabalawy
authors.forename: John A
authors.initials: JA
authors.lastname: Wilkins
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000378:metabolism; D002888:Chromosomes, Human, Pair 19; D015180:Electrophoresis, Gel, Two-Dimensional; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D010003:Osteoarthritis / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D040901:Proteomics; D017386:Sequence Homology, Amino Acid; D013582:Synovial Fluid / Q000737:chemistry; D013583:Synovial Membrane / Q000166:cytology / Q000378:metabolism*
chemical_list: D011506:Proteins