A Stride Forward for Knee Repair

Athletes can live with muscle strains, but a torn ligament or tendon is serious business. Each year, surgeons in the United States perform about 500,000 operations on tendons and ligaments, which usually heal slowly and incompletely. But faster, better healing may be on the way: A report in today's Journal of Clinical Investigation describes proteins that, at least in rats, promote the growth of these connective tissues.

The findings emerge from studies of bone repair. For years, Vicki Rosen and colleagues at the Genetics Institute Inc., in Cambridge, Massachusetts, have been experimenting with proteins that induce undifferentiated stem cells to divide and form new bone. They have produced the factors using recombinant DNA technology and implanted them under the skin and into muscles of rats, where they cause new bone tissue to form. Doctors have also successfully used these factors as an experimental treatment for serious bone fractures in more than 1000 human patients worldwide.

During their investigations on rats, Rosen's team was surprised to find that three proteins in the bone-inducing family--called growth and differentiation factors 5, 6, and 7--triggered growth of what appeared to be connective tissue, not bone. Under the electron microscope, for example, they found the induced tissues "showed a highly ordered arrangement of collagen bundles," forming fibers about the size of those found in tendons and ligaments. "These proteins might have a really significant ability to repair injured tendons and ligaments," Rosen says.

The work has impressed experts, including Marshall Urist of the University of California, Los Angeles, who discovered bone-inducing factors over 30 years ago. If confirmed, these new growth and differentiation factors could lead to great advances in orthopedic surgery, he says: "In the 21st century, surgeons may be using them for repair of tendons and ligaments."