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Localisation of fibronectin mRNA in the rheumatoid synovium by in situ hybridisation
H A Waller1, M G Butler, J G McClean
1Department of Rheumatology, St Bartholomew's Hospital Medical College, London, United Kingdom.
Abstract:
The distribution of fibronectin, an extracellular matrix glycoprotein which plays a part in fibrosis and tissue repair, has previously been described using immunohistochemical methods. These do not differentiate between locally synthesised and plasma derived fibronectin. In this work the distribution of cells actively synthesising fibronectin was assessed by in situ hybridisation using a radiolabelled antisense RNA probe in synovial biopsy samples from patients with rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, and control subjects without inflammatory disease. Large amounts of fibronectin mRNA were found specifically in synovial lining cells, providing evidence for the local production of fibronectin in the synovium. Levels of fibronectin mRNA were variable between patients. These differences were not related to the diagnosis or to the subintimal inflammatory cell infiltrate; where there was synovial lining cell hyperplasia there was a concomitant increase in the number of cells containing fibronectin mRNA, which was consistent with increased levels of immunoreactive fibronectin at this site. Increased levels of fibronectin in synovial fluid in patients with rheumatoid arthritis may be due to an increased number of lining cells secreting the protein, rather than upregulation of the gene by these cells.
Insights
This study reveals that synovial lining cells actively synthesize fibronectin, a key protein in tissue repair. Increased fibronectin in rheumatoid arthritis may stem from more lining cells producing it, not increased gene activity.
Area of Science:
- Biochemistry
- Immunology
- Rheumatology
Background:
- Fibronectin, an extracellular matrix glycoprotein, is crucial for fibrosis and tissue repair.
- Previous methods could not distinguish between locally synthesized and plasma-derived fibronectin.
- Understanding fibronectin's local production is vital for inflammatory joint diseases.
Purpose of the Study:
- To determine the distribution of cells actively synthesizing fibronectin in the synovium.
- To investigate the local production of fibronectin in various arthritic conditions.
- To clarify the source of increased fibronectin in synovial fluid.
Main Methods:
- In situ hybridization using a radiolabeled antisense RNA probe.
- Analysis of synovial biopsy samples from patients with rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, and controls.
- Quantification of fibronectin mRNA in synovial lining cells.
Main Results:
- Significant fibronectin mRNA expression was localized to synovial lining cells, indicating local fibronectin production.
- Fibronectin mRNA levels varied between patients and were not directly correlated with diagnosis or inflammatory infiltrate.
- Synovial lining cell hyperplasia correlated with an increased number of fibronectin mRNA-containing cells and local fibronectin levels.
Conclusions:
- Synovial lining cells are a primary source of local fibronectin synthesis in the synovium.
- Elevated synovial fluid fibronectin in rheumatoid arthritis is likely due to an increased number of fibronectin-secreting lining cells.
- The findings suggest hyperplasia of synovial lining cells, rather than gene upregulation, drives increased fibronectin in certain arthritic conditions.