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Intra-articular tissue factor/factor VII complex induces chronic arthritis
M I Bokarewa1, J Morrissey, A Tarkowski
1Department of Rheumatology and Inflammation Research, Sahlgrenska University Hospital, Göteborg, Sweden. maria.bokarewa@rheuma.gu.se
Summary
Tissue factor (TF)/factor VII (FVII) complexes in joint fluid contribute to rheumatoid arthritis (RA) pathogenesis. These complexes induce inflammation and joint destruction, suggesting they are key drivers in chronic destructive arthritis.
Area of Science:
- Rheumatology
- Immunology
- Biochemistry
Background:
- Fibrin accumulation in joints is characteristic of chronic arthritides like rheumatoid arthritis (RA).
- Tissue factor (TF)/factor VII (FVII) complex formation initiates fibrin production, a key process in joint inflammation.
Purpose of the Study:
- To investigate the role of the TF/FVII complex in the pathogenesis of joint inflammation.
- To quantify TF/FVII complex levels in RA patients' synovial fluid and assess its effects in a mouse model.
Main Methods:
- Measured TF/FVII complex levels in synovial fluid from RA patients.
- Injected TF/FVII complex intra-articularly into healthy mice to observe joint responses.
- Analyzed joint morphology, cellular infiltration, and inflammatory markers post-injection.
Main Results:
- TF/FVII complex injection in mice induced significant mononuclear leukocyte influx, cartilage, and bone destruction.
- TF/FVII complex triggered more severe and prolonged arthritis than individual components.
- TF/FVII complexes were detected in 20 out of 40 RA patients' synovial fluid samples.
Conclusions:
- TF/FVII complexes are frequently present in RA joints.
- These complexes play a crucial role in initiating and perpetuating chronic destructive arthritis.
- TF/FVII complexes represent a potential therapeutic target for managing RA.