Two Proteins Join Forces to Form Bone

If one bone-repairing protein does not work as you want it to—pair it with another. That is what researchers at UCLA did with the bone morphogenetic protein BMP2—an FDA approved bone healing protein. Unfortunately, the high doses of BMP2 that were required to induce human bone formation also caused swelling and inconsistent and inappropriate bone growth.

Now introduce the second protein NELL-1 which was discovered by Kang Ting, D.M.D., D.Med.Sc, professor and chair of the section of orthodontics at the UCLA School of Dentistry. When the two proteins are brought together there is increased bone formation. In addition, NELL-1 inhibited the formation of fat cells—a negative side effect of BMP2. The researchers found that NELL-1 encouraged stem cells to form bone cells instead of fat cells. Used together, the two proteins stimulate bone production more dramatically 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, ” Ting said. “The combination of NELL-1 and BMP2 improved safety and efficacy of bone regeneration in animal models—and may, one day, offer patients significantly better bone healing.”

The study showed that NELL-1 works 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 induce non-bone cells to form bone, with the potential risk for ectopic bone growth—bone formation in undesirable locations.

The researchers found that the two proteins complement each other. The BMP2 helps to turn non-bone cells into bone-forming cells, and NELL-1 increases the bone-forming ability of bone cells. One of the investigators, Chia Soo, M.D., professor of plastic surgery and vice chair for research at the David Geffen School of Medicine at UCLA, said, “ 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.”

The study will appear as the lead article in the February edition of the American Journal of Pathology.