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- Title
Silencing of protease-activated receptors attenuates synovitis and cartilage damage following a joint bleed in haemophilic mice.
- Authors
Nieuwenhuizen, L.; Schutgens, R. E. G.; Coeleveld, K.; Mastbergen, S. C.; Schiffelers, R. M.; Roosendaal, G.; Biesma, D. H.; Lafeber, F. P. J. G.
- Abstract
Introduction and aim Joint bleeding results in blood-induced arthropathy. We investigate whether a joint bleed alters protease-activated receptor ( PAR) expression, and whether treatment with small interfering RNA (siRNA) targeted against PAR1-4 attenuates synovitis and cartilage damage. Methods Protease-activated receptor expression was evaluated upon a joint bleed in haemophilic mice and in humans. In addition, mice with a joint bleed were randomized between treatment with PAR1-4 siRNA or control and evaluated for the presence of synovitis and cartilage damage. Also, human cartilage was transfected with PAR1-4 siRNA or control, and evaluated for plasmin-induced cartilage damage. Results Following a joint bleed, we observed an increase in synovial PAR1, -2 and -4 expression, and an increase in chondrocyte PAR2 and -3 expression in mice (all P < 0.05). Also an increase in synovial PAR1 and chondrocyte PAR4 expression in patients was observed (both P < 0.05). Treatment of a joint bleed in haemophilic mice with PAR1-4 siRNA attenuates synovitis and cartilage damage (both P < 0.01). Treatment of human cartilage tissue explants with PAR1-4 siRNA reduced plasmin-induced cartilage damage ( P < 0.01). Conclusion This study demonstrates that synovial and chondrocyte PAR expression is altered upon a joint bleed, and that treatment with PAR1-4 siRNA attenuates synovitis and plasmin-induced cartilage damage.
- Subjects
PROTEASE-activated receptors; SYNOVITIS; CARTILAGE diseases; JOINT diseases; HEMOPHILIA; SMALL interfering RNA
- Publication
Haemophilia, 2016, Vol 22, Issue 1, p152
- ISSN
1351-8216
- Publication type
Article
- DOI
10.1111/hae.12770