Protein Dip Speeds Bone Growth

Bone fractures in the elderly are slow to heal. Now researchers at Stanford University School of Medicine have come up with a simple and effective way to speed up the growth of healthy new bone. As explained by Stanford University writer Krista Conger, researchers have found that a quick immersion in a signaling protein solution called Wnt3a can speed up the growth of healthy bone in response to a break.

If this simple treatment works on humans, it will improve the outcomes of the more than 500, 000 bone grafts performed each year in the U.S. “We’re very focused on designing a treatment that could be easily employed by orthopaedic surgeons in the normal course of bone grafting, ” said professor of surgery Jill Helms, D.D.S., Ph.D.

Bone grafting involves transplanting whole marrow—which is rich in stem cells that form bone, blood and the cells of the immune system—into a fracture site. Doctors prefer using a patient’s own marrow to avoid the problem of rejection. Unfortunately, marrow from older patients does not work like marrow from younger patients does. So orthopedic surgeons often use donor bone or marrow and rely on drugs to stimulate bone growth. The hope is to find alternatives that allow the use of a patient’s own cells without medications.

They may have found it. The researchers discovered that a quick dip in a bath of a signaling protein called Wnt3a can rev up sluggish bone-forming cells in older animals that would normally be unable to heal a fracture. “We’ve shown that when we temporarily treat bone marrow from aged animals with Wnt before transplanting the cells into a fracture site, we see really robust bone formation, ” said Helms.

In the current study, Conger explained, the researchers harvested bone marrow from laboratory mice genetically engineered to express a fluorescent protein. They then transplanted this marrow into 2-millimeter holes they’d created in the skulls of anesthetized mice and followed the fate of the transplanted cells.

Within seven days, the transplanted marrow cells had begun to divide. The defects in the mice that had received the treated bone graft healed completely while the untreated mice were unable to fill the hole with new bone.

When the researchers repeated the experiment with marrow from older animals they found that they generated much less bone at the site of the injury. The older animals also expressed lower levels of the Wnt protein than did the younger ones. The researchers exposed the aged donor marrow to a brief bath of either Wnt3a or a control solution before transplanting them into the recipients. Within seven days, animals that received the Wnt-treated marrow had twice as much new bone at the injury site as did the control animals.

The researchers then repeated their experiments on rabbits, which have longer bones that more closely resemble those of humans. Again, they found that treating old marrow briefly with Wnt3a significantly improved the cells’ ability to heal a fracture in the leg. Helms is the senior author of the study, published in July in the Journal of Bone and Joint Surgery. Philipp Leucht, M.D., a resident in orthopedic surgery at Stanford, is the lead author.