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Summer 2007

Stop-loss: Halting Post-traumatic Cartilage Damage

Hyaline cartilage does not tolerate trauma well. The immediate damage from acute trauma will affect cartilage just as any tissue, but what happens afterward may make things much worse.

Cartilage cells surrounding areas of injured cartilage body are prone to self-destruct through a process termed programmed cell death, or "apoptosis." "We were the first research group to show that high levels of apoptosis are associated with osteochondral fractures in humans," says UCSF orthopaedic surgeon Hubert Kim, M.D., Ph.D. "After injury, you may find half the nearby cartilage cells undergoing apoptosis."

Hyaline cartilage that dies does not regenerate. Discovering a way to keep injured cartilage cells from dying after trauma or surgery may go a long way toward preventing or forestalling cartilage degeneration.

Kim has been leading an effort at UCSF to find drugs that might interrupt the self-destructive response to injury that cartilage cells manifest.

Such efforts already have a long history. In stroke and spinal cord injury, as with cartilage, much of the cell damage is secondary, occurring after the initial injurious event. Many companies have spent a lot of time trying to discover enzymatic inhibitors that would limit the secondary neural damage after stroke. Similar inhibitors might ultimately be useful in emergency rooms to save cartilage after traumatic injury. "We are interested in some of the same molecules that people are studying for spinal cord injury," Kim says.

Another arena for such intervention is after surgery. Simply cutting cartilage during repair procedures will lead to cell death at the margins of the incision. Currently, even grafting in completely healthy cartilage will lead to weakened cartilage at the margins of the repair.

Kim currently has a grant to investigate drugs that may salvage injured cartilage. "We have identified several drugs that can rescue cartilage cells from programmed cell death in animal models. In the near future, we plan on testing this approach to see if it can help patients with cartilage injuries," Kim says.

Hubert Kim can be contacted at (415) 353-2808.

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