Mitochondrial Based Treatments that Prevent Post-Traumatic Osteoarthritis in a Translational Large Animal Intraarticular Fracture Survival Model
Annual rept. 1 Sep 2012-31 Aug 2013
IOWA UNIV IOWA CITY
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The purpose of this research is to investigate a novel therapeutic approach to preventing PTOA by addressing mitochondrial dysfunction and oxidative damage in cartilage. Thus far we have tested a number of compounds for therapeutic activity in a chondral injury model that involves a high energy impact to the medial femoral condyle of rabbits. The selection of compounds included an oxidant scavenger, N-Acetylcysteine, a drug that reduces mitochondrial superoxide production by blocking electron flow through complex I amobarbital, and two drugs that block actin and tubulin remodeling cytochalasin B and nocodazole respectively. Treatments were administered acutely after injury N-acetyl cysteine and amobarbital or prior to injury cytochalasin B and nocodazole. At seven days post-op the rabbits were euthanized and the injured cartilage was analyzed for viability, and ATP. While NAC at a low dose was effective in preventing injury-related chondrocyte losses, amobarbital, nocodazole, and cytochalasin B were more effective at sparing metabolic activity. With these data in hand we are ready to go forward with the long-term rabbit study, in which we will determine the effects of amobarbital and nocodazole on cartilage degeneration Aim 2. The most effective treatment will be tested in a porcine intraarticular fracture model Aim 3.
- Medicine and Medical Research