Nieuwenhuizen L, Schutgens R E G, Coeleveld K, Mastbergen S C, Schiffelers R M, Roosendaal G, Biesma D H, Lafeber F P J G
Rheumatology and Clinical Immunology, University Medical Center, Utrecht, The Netherlands.
Hematology and Van Creveldkliniek, University Medical Center, Utrecht, The Netherlands.
Haemophilia. 2016 Jan;22(1):152-9. doi: 10.1111/hae.12770. Epub 2015 Jul 20.
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.
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.
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).
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.
关节出血会导致血液性关节病。我们研究关节出血是否会改变蛋白酶激活受体（PAR）的表达，以及用针对PAR1 - 4的小干扰RNA（siRNA）进行治疗是否能减轻滑膜炎和软骨损伤。
在血友病小鼠和人类中，于关节出血后评估蛋白酶激活受体的表达。此外，将关节出血的小鼠随机分为接受PAR1 - 4 siRNA治疗组或对照组，并评估滑膜炎和软骨损伤情况。同时，用PAR1 - 4 siRNA或对照转染人软骨，并评估纤溶酶诱导的软骨损伤情况。
关节出血后，我们观察到小鼠滑膜PAR1、-2和-4表达增加，软骨细胞PAR2和-3表达增加（均P < 0.05）。患者中也观察到滑膜PAR1和软骨细胞PAR4表达增加（均P < 0.05）。用PAR1 - 4 siRNA治疗血友病小鼠的关节出血可减轻滑膜炎和软骨损伤（均P < 0.01）。用PAR1 - 4 siRNA处理人软骨组织外植体可减少纤溶酶诱导的软骨损伤（P < 0.01）。
本研究表明，关节出血后滑膜和软骨细胞的PAR表达会发生改变，且用PAR1 - 4 siRNA治疗可减轻滑膜炎和纤溶酶诱导的软骨损伤。
