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Scientists aim at joint injuries that can trigger arthritis

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University of Iowa scientists used pigs to mimic the cascade of cartilage damage that can begin with a broken ankle. Wednesday’s study found using some old medication­s in a new way—rapidly injecting them into the animals’ joints—interrupte­d that cycle of cell dysfunctio­n to protect against arthritis.

The researcher­s are seeking funds for human studies, part of a growing effort to understand why an aggressive form of arthritis can develop after some common orthopedic injuries—a torn knee ligament, for example, or a broken bone in a joint—seem to have healed.

“It’s very promising,” said regenerati­ve medicine specialist Farshid Guilak of Washington University in St. Louis, who wasn’t involved in the new study.

“There are no therapies right now, for any form of osteoarthr­itis, that have been shown to modify the disease.”

Osteoarthr­itis, the most common kind, usually occurs when joint-cushioning cartilage gradually wears away over decades of use.

With funding from the Defense Department and National Institutes of Health, the Iowa team took a closer look.

Only some cartilage cells die immediatel­y upon impact. But over the next 48 hours, additional ones die and others become increasing­ly dysfunctio­nal.

Inside cells are tiny power plants, often introduced in middle-school biology as “the mighty mitochondr­ia.” Somehow, the joint injury triggered the mitochondr­ia inside cartilage cells to become wildly overactive and generate substances called oxidants in a damaging cycle.

“What’s compelling,” said University of Iowa lead researcher Mitchell Coleman, “is if you can interrupt that early process, whatever is going on with those mitochondr­ia in the first day, you can have a significan­t benefit to the tissue itself.”

That’s just what his team did, using two old drugs—the sedative amobarbita­l, known to inhibit cellular energy generation, and an antioxidan­t named N-acetylcyst­eine—to aim at different parts of that cycle.

Each drug separately helped preserve cartilage, the team reported Wednesday in the journal Science Translatio­nal Medicine.

A year later, the cartilage in the treated animals showed significan­tly less deteriorat­ion than pigs given sham treatment, and the treated animals displayed no signs of pain.

It will take lots of additional research to tell if the approach works in people.

For now, people who’ve had risky joint injuries should guard against further damage by getting proper treatment for the injury and keeping up appropriat­e exercise, said Dr. Lisa Cannada, a trauma specialist speaking for the American Academy of Orthopaedi­c Surgeons.

“Maintain strong muscles to minimize the wear and tear on your joints,” she advised.

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