Presented at the 2017 ORS Annual Meeting, this study evaluated whether early inhibition of mitochondrial complex I can reduce the rapid onset of posttraumatic osteoarthritis (PTOA) following intra-articular fracture (IAF). Building on earlier in vitro research, the team tested two interventions:
- Amobarbital — a reversible complex I inhibitor
- N-acetylcysteine (NAC) — a thiol antioxidant that reduces oxidative stress
Using a clinically realistic porcine fracture model and human-like ORIF fixation, researchers delivered either amobarbital, NAC, or vehicle control directly into the joint following injury.
Key Findings
- Complex I inhibition (>90%) was confirmed following amobarbital administration.
- NAC prevented intracellular thiol oxidation, reducing oxidative stress one week after injury.
- Fracture + ORIF alone led to significant cartilage degeneration, increased Mankin scores, reduced safranin O staining, and focal eburnation.
- Both amobarbital and NAC groups showed statistically significant reductions in Mankin scores compared to controls.
- Treated animals demonstrated thicker cartilage, better proteoglycan retention, and healthier overall histology at six months.
Significance
These findings highlight mitochondrial oxidant production as a key driver of early PTOA initiation, and identify a therapeutic window immediately after joint injury where metabolic intervention may meaningfully alter disease progression. The study supports continued development of early biologic treatments aimed at preserving cartilage following traumatic joint injury.