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Published on: May 10, 2020
Synoviocytes synthesize, bind, and respond to basic fibroblast growth factor
V O Melnyk1, G D Shipley, M D Sternfeld
1Department of Medicine, Oregon Health Sciences University, Portland 97201.
Synoviocytes in rheumatoid arthritis (RA) produce basic fibroblast growth factor (bFGF), a key driver of cell proliferation. This finding suggests bFGF from synoviocytes fuels RA pathogenesis through autocrine signaling.
Area of Science:
- Rheumatology
- Cell Biology
- Molecular Medicine
Background:
- Rheumatoid arthritis (RA) involves destructive synovial tissue proliferation, resembling malignancy.
- The role of growth factors in non-neoplastic proliferative diseases like RA is understudied.
Purpose of the Study:
- To investigate if synoviocytes are a source of growth factor activity in RA.
- To determine the specific growth factor involved in synoviocyte proliferation.
Main Methods:
- Assessed mitogenic activity in synoviocyte culture supernatants from RA, osteoarthritis, and traumatic joint disease patients.
- Characterized the biological properties of the mitogenic activity, including synergy with insulin and heparin-binding elution profiles.
- Analyzed synoviocyte extracts for peptides reacting with bFGF antibodies and assessed gene/receptor expression.
Main Results:
- Synoviocyte supernatants exhibited mitogenic activity identical to basic fibroblast growth factor (bFGF).
- Identified a ~16,000 MW peptide in synoviocytes reactive to anti-bFGF antibodies.
- Demonstrated that cultured synoviocytes express bFGF, its receptors, and proliferate in response to bFGF.
Conclusions:
- Synoviocytes are a source of bFGF activity.
- Autocrine bFGF signaling by synoviocytes likely contributes to RA pathogenesis and synovial proliferation.
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