Scientists see protein's bone-building potential

Tuesday, April 16, 2002

PITTSBURGH -- Research-ers are testing whether a protein that powers bone growth in the body can be harnessed to jump-start healing and possibly eliminate painful and intensive surgeries such as bone grafts.

The protein, known as Runx or core binding factor A, has been called the "master switch" for bone-making cells, called osteoblasts. In studies, researchers have found that mice genetically engineered to lack the protein didn't form bones.

"If this protein can have such an impact on the formation of a skeleton, why can't we harness this power as a clinical therapy?" said Jeffrey Hollinger, head of Carnegie Mellon University's recently opened Bone Tissue and Engineering Center.

Scientists are trying to figure out if the protein can be used to initiate bone growth in the body.

Researchers say stimulating the body to grow its own bone is preferable to invasive, costly and painful surgery to graft bone from another part of a patient or using bones from cadavers. Grafting can lead to infections and blood loss, while bones from cadavers can be rejected or transmit diseases.

Plastic, metal or ceramic replacements are used in other cases, but they don't grow with patients and can't adapt the way living bone can.

Seeded with protein

Bone tissue engineering often involves implanting a biodegradable material in the shape of the desired bone seeded with a bone-growing protein or hormone. Osteoblasts then attach themselves to the material and form new bone as the material dissolves.

The Food and Drug Administration is evaluating other proteins, called bone morphogenetic proteins or BMPs, that have been shown to stimulate bone growth.

And there is other research which shows parathyroid hormone, which regulates the amount of calcium in the body by affecting the kidneys, intestine and bones, can repair bones and can double bone growth in people with osteoporosis.

The Pittsburgh effort, however, could give patients another option and, according to researchers, fine-tune bone engineering.

Unlike BMPs or parathyroid hormone, researchers believe Runx would only affect bone cells and only in small areas. BMPs can influence fat, scar tissue and cancer cells and too much parathyroid hormone which can cause damage, research-ers say.

"I would rather be treated with a treatment that does one thing rather than one that can do a number of things," Hollinger said.

Early stages

Pittsburgh researchers are in the early stages of testing and say they have used Runx in laboratory cultures to trigger cells predisposed to being bone-making cells into osteoblasts. They expect to begin animal trials within weeks.

The center has received a $1.5 million grant from the National Institutes of Health and $2.2 million from the National Institute of Standards and Technology to study the protein.

But one researcher said the Pittsburgh effort could be unnecessary if the Food and Drug Administration approves BMPs for use in patients.

"I don't know why you want to use it given BMPs. If insulin works for diabetes, why do you need to find another insulin?" said Dr. Scott D. Boden, a professor of orthopedic surgery at Emory School of Medicine in Atlanta.

While Runx is necessary for bone formation, it may not be enough to form bone by itself, said Boden, who worked on one of two versions of BMP.

Hollinger said that is what he hopes to find out.

"It might be a better solution, it may be a flat tire, but we don't know," Hollinger said.

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