UC Researchers Find Protein That Speeds Healing of Bones
A previously unknown protein that stimulates bone healing has been discovered by researchers at the UC San Francisco School of Dentistry.
The new material, called osteogenic growth factor, joins a list of at least five other protein hormones that have been found to stimulate bone growth.
Two of the new materials are already being tested in humans to speed the healing of fractured bones or to stimulate regrowth of bones that have been lost to cancer or during plastic surgery. Such research suggests that possibilities for repair of bone defects may soon be expanded markedly.
Loss in Space
Work with the substances is also helping to explain why astronauts lose bone mass in space and how an electrical field can promote bone healing.
Dr. Richard Kao reported the discovery of osteogenic growth factor Friday at a meeting of the American Assn. for Dental Research in Washington. He said the protein is isolated from demineralized ground bone and affects a specific phase of bone growth.
“The bone healing cycle is characterized by a very long phase in which new bone cells, or osteoblasts, are exceptionally slow in multiplying,” Kao said in a telephone interview. Osteogenic growth factor shortens this period by about half.
“We absorbed (the factor) in sponges and implanted them in holes drilled in the legs and mandibles (jaws) of rats,” Kao said, “and observed a greatly increased rate of healing.”
Kao’s protein is the newest foot soldier in what is beginning to seem like a small army of agents that can affect bone growth. “Army” is an appropriate choice of terms because bone is a tissue that is constantly at war with itself.
“Bone has two opposing--and almost contradictory--functions,” according to Dr. David J. Baylink of Loma Linda University. “It has to have a good mass to serve as a structural support for the body, and it has to serve as a mineral reservoir to provide calcium when it is needed elsewhere in the body.”
‘A Way to Protect Itself’
But when calcium is removed from the bones, they become fragile and brittle, a condition known as osteoporosis. Such brittleness is particularly common among older women and diabetics.
It appears that bone has evolved the growth-stimulating agents “as a way to protect itself from the rest of the body,” Baylink explained.
The first bone growth stimulator, called bone morphogenetic protein or BMP, was discovered in 1965 by Dr. Marshall R. Urist of UCLA.
BMP induces certain types of connective tissues and other unspecialized cells to become bone cells. Implanted in muscle tissue, for example, BMP will stimulate the conversion of connective tissue to an amorphous mass of bone. Implanted at the site of a fracture, however, BMP will cause the fracture to heal more rapidly.
Urist said BMP is being tested in patients with large bone defects caused by injury, infections, removal of tumors and congenital malformation.
The chief problem with the material, he added, is that it is now available only in limited quantities. His group is trying to produce more of the hormone through genetic engineering techniques.
BMP is unusual in that it, alone among agents so far discovered, appears to be specific for bone cells. All of the other agents, including that discovered by Kao, fall in the more general category of substances that increase the division of all healing tissues.
Four other groups have isolated bone growth promoters. But they do not have enough of the hormones to conduct clinical trials.
At Children’s Hospital Medical Center in Boston, researchers Julie Glowacki and Judah Folkman have devised a way to overcome that problem by making a paste of ground demineralized bone, forming it into specific shapes, and implanting it in a patient’s body.
350 Patients Treated
The ground bone matrix stimulates production of new bone around it, presumably because the bone releases one or more of the growth-promoting hormones. Glowacki and Folkman have so far treated more than 350 patients with the same types of problems as those treated by Urist.
The research with bone growth hormones is also providing insight into some previously mysterious processes. Baylink has recently found, for example, that when bone cells growing in the laboratory are exposed to an electrical field, they secrete a bone growth promoter.
This discovery provides the first explanation of why it is possible to stimulate bone healing by application of an electric field through implanted electrodes.
Baylink also notes that the jarring of bones during walking is known to create a minute electrical field, while jogging creates a somewhat bigger field. This may explain, he said, why jogging stimulates increased bone density in the runners’ legs.
The constant application of the small field created during walking may also be necessary to maintain sufficient bone density, he argued. The fact that astronauts do not walk in space may thus explain why the density of their bones is reduced while they are in space.
