A team of UCLA researchers has found a combination of proteins, which could significantly improve clinical bone restoration. The findings may lead to the development of effective new treatments for bone defects, bone loss, and osteoporosis. The findings were published in the February edition of the American Journal of Pathology.
The study was led by Kang Ting, D.M.D., D.Med.Sc., professor and chair of the section of orthodontics at the UCLA School of Dentistry, Dr. Chia Soo, M.D., professor of plastic surgery and vice chair for research at the David Geffen School of Medicine at UCLA, and Aaron James, M.D., a fellow in surgical pathology. They used bone morphogenetic protein-2 (BMP2), which is an FDA-approved bone-healing protein. The new research is based on other studies of bone growth, including one that utilized a protein called NELL-1, which successfully increased bone formation and stimulated key factors for bone growth in multiple research models.
In the new study, the researchers combined the NELL-1 protein, which Dr. Ting discovered, with BMP2. They found that the combination of the two proteins promoted bone formation and inhibited the formation of fat cells; this inhibition was a negative side effect of BMP2, which encourages stem cells to form both bone and fat cells. In contrast, NELL-1 encourages stem cells to form bone cells instead of fat cells. Used together, the two proteins stimulate bone production more significantly than either does alone.
“Before this study, large bone defects in patients were difficult to treat with BMP2 or other existing products available to surgeons,” noted Dr. Ting. He added, “The combination of NELL-1 and BMP2 resulted in improved safety and efficacy of bone regeneration in animal models — and may, one day, offer patients significantly better bone healing.” The new study revealed that NELL-1 functions by activating the cellular signaling pathway that regulates whether a stem cell differentiates into a bone cell or a fat cell. It also showed that BMP2 can stimulate non-bone cells to form bone, with the potential risk for ectopic bone growth (bone formation in undesirable locations).
The two proteins complement each other in that BMP2 helps convert non-bone cells into bone-forming cells, and NELL-1 then increases the bone-producing ability of bone cells. “In contrast to BMP2, the novel ability of NELL-1 to stimulate bone growth and repress the formation of fat may highlight new treatment approaches for osteoporosis and other therapies for bone loss,” explained Dr. Soo.
NELL-1 is also currently under development as a single therapy for the systemic treatment of osteoporosis. NELL-1, when given systemically, does not appear to induce ectopic bone formation. In contrast, because of its known ability to induce unwanted bone, BMP2 may not be as appropriate for systemic administration.