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A Peptide from Thrombospondin 1 Modulates Experimental Erosive Arthritis by Regulating Connective Tissue Growth Factor



Details

  • Personal Author:
  • Description:
    Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with leukocyte adhesion to and extravasation through vascular endothelium into synovial tissue. Recent evidence indicates that the thrombospondin 1 gene is up-regulated in patients with RA. We have identified a region within the TSP-1 type 3 repeats that inhibits human neutrophil elastase (HNE) and binds to human neutrophils. The present study was undertaken to investigate the therapeutic benefit of this TSP-1-derived peptide sequence and its effect on connective tissue growth factor (CTGF), a protein involved in fibrotic disorders and in neovascularization, which is a hallmark of RA. CTGF gene and protein expression, as well as protein levels of CTGF in the synovium, after treatment with the TSP-1-derived peptide were studied in the peptidoglycan-polysaccharide animal model of erosive arthritis. Peptide treatment prevented joint infiltration and inflammation and was associated with reduced circulating antigen levels of HNE and TSP-1. Additionally, CTGF was up-regulated in this experimental model of RA. Treatment with the TSP-1-derived peptide was associated with down-regulation of the message and protein levels of CTGF. Immunofluorescence studies showed that the mean area fraction of CTGF immunoreactivity in the peptide-treated group of animals was significantly less than that in the untreated group. These results document a role for TSP-1 in regulating CTGF gene and protein expression in synovial tissue, suggesting a link with the disease course in this model of RA. This TSP-1-derived synthetic peptide may represent an important template for drug development in RA and other inflammatory conditions associated with neutrophil activation. [Description provided by NIOSH]
  • Subjects:
  • Keywords:
  • ISSN:
    0004-3591
  • Document Type:
    Text
  • Funding:
    Grant
  • Genre:
    Journal Article
  • Place as Subject:
  • CIO:
    National Institute for Occupational Safety and Health (NIOSH)
  • Topic:
    Workplace Safety & Health
  • Location:
    North America
  • Volume:
    54
  • Issue:
    8
  • NIOSHTIC Number:
    nn:20030981
  • Citation:
    Arthritis Rheum 2006 Aug; 54(8):2415-2422
  • Contact Point Address:
    Joanne M. Manns, Temple University School of Medicine, Department of Physiology 230 B OMS, 3400 North Broad Street, Philadelphia, PA 19140
  • Email:
    mannsjm@temple.edu
  • Federal Fiscal Year:
    2006
  • NORA Priority Area:
    Disease and Injury: Musculoskeletal Disorders of the Upper Extremities
  • Performing Organization:
    Temple University
  • Peer Reviewed:
    True
  • Start Date:
    20000601
  • Source Full Name:
    Arthritis and Rheumatism
  • End Date:
    20120731
  • Collection(s):
  • Main Document Checksum:
    urn:sha-512:e8835b437abad398fc22d8685d9f22b4b50be3750977ad4339d86a27e0a535691e277891ad3bc9f2d79dc1658dcb699811d506aa54a949a1ac88d5d9551debb1
  • Download URL:
  • File Type:
    Filetype[PDF - 509.57 KB ]
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