Investigating contributions of hydrogen peroxide to radiation-induced arthrofibrosis

As cancer survivorship increases, the number of patients suffering from radiation therapy-induced injuries will continue to grow. It is important to study the debilitating and often painful aftereffects of radiation therapy if patients are to have a good quality of life following their treatment. Radiation-induced arthrofibrosis is a disease that affects joints that were exposed to radiation doses during cancer therapy and usually manifests as collagenous bands of fibrous tissue that reduce the range of motion and make movement in the joint painful. Not many therapies are available to patients suffering from arthrofibrosis. Forced mobilization under anesthesia, or surgical resection, each followed by physical therapy, create additional wounds in the affected joint that are likely to have recurrent fibrosis. A mouse model was developed to study the initiation and progression of this disease. This model showed a potential therapeutic window at around 8 weeks after therapy, and immunohistochemistry on stifle joints suggested that the fat pad is a critical signaling area, as markers for fibrosis and oxidative damage were increased in the fat. Using immortalized preadipocyte cells, or adipose stem cells, we examined the effect of radiation and hydrogen peroxide based oxidative stress on adipogenesis. Radiation doses and continuous exposure to hydrogen peroxide were able to decrease the adipogenic capacity of these cells, which was rescued by catalase overexpression. These findings identify fat tissue as an important tissue to spare during radiation treatment planning, and the 8-week window following radiation therapy as a critical time to treat affected joints to prevent fibrosis.