Introduction Hemophilia is a congenital bleeding disorder due to the deficiency of blood coagulation factor VIII or IX. The joint is the most common site of serious bleeding. Repeated episodes of hemarthrosis lead to hemophilic synovitis (HS) and destructive hemophilic arthropathy (HA). The molecular changes responsible for HS and HA are not known. Osteopontin (OPN) has been implicated in the process that leads to bone destruction in other forms of arthritis. We hypothesized that OPN plays a similar role in HA.
Methods Hemophilic synovitis was induced in factor (F) VIII and IX deficient mice by causing traumatic (blunt trauma) and non-traumatic (needle puncture) hemarthrosis in the right knee joint of mice. The concentration of OPN was measured in plasma of mice five days after inducing hemorrhage. Expression of OPN in synovial tissue from affected knee joints was compared with control uninjured joints by DNA microarray and semi-quantitative RT-PCR analysis on different days following joint injury.
Results OPN concentration in the plasma of both FVIII and FIX deficient mice sacrificed 5 days after a single capsular puncture was increased 92–98% compared to control mice. In other experiments, traumatic hemarthrosis was induced three times at weekly intervals in the right knee joints of FVIII deficient mice. On day 21, synovial tissue from the knee joints of 20 mice was isolated, pooled and RNA from affected and control joints probed using microarray. The expression of OPN in right knee tissue was 7.5-fold greater compared to the left. These data were confirmed by RT-PCR analysis which showed that OPN was highly expressed in synovial tissue from mice 14, 21 and 30 days after single puncture injury and 21 days following three traumatic injuries.
Conclusion The concentration of OPN was increased in the plasma of mice following hemarthrosis and OPN expression was increased 7-fold in synovial tissue of mice with hemophilic arthropathy. Our data implicate OPN in the pathobiology of hemophilic arthropathy.
Disclosure: No relevant conflicts of interest to declare.