Targeting mitochondria, the tiny power plants inside of cells, after injury could help protect joints from cartilage loss, scientists report. The strategy may help stave off the progressive cartilage destruction that frequently happens after people break bones in their joints - a condition known as posttraumatic osteoarthritis (PTOA), which compromises quality of life for more than 5.6 million Americans every year and has no existing treatments. Fractures expose the delicate tissue inside joints to a rush of oxygenated blood and inflammatory compounds, which Mitchell Coleman et al. speculated could cause a burst of activity by mitochondria inside cartilage cells. To prevent overactive mitochondria from producing harmful reactive oxygen species, the scientists used a compound called amobarbital, a sedative sometimes used to treat anxiety that also inhibits cellular energy generation. The researchers mixed amobarbital into a heat-activated hydrogel that is liquid at room temperature, then solidifies inside the joint to ensure delivery of the compound to the injury site. Injections of the amobarbital gel (or another inhibitor of mitochondrial function called NAC) into the ankles of minipigs (which are anatomically similar to human ankles) with surgically-stabilized joint fractures protected the animals from the cartilage-destroying effects of PTOA. One year after injury, the cartilage in the treated animals' ankles was less deteriorated compared to controls, and the animals didn't show evidence of arthritic pain. Coleman and colleagues further confirmed that amobarbital was not toxic to human cartilage cells in culture, and they say their findings suggest targeting mitochondria after joint fractures might substantially improve quality of life for PTOA patients.
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Journal
Science Translational Medicine