Molecules that Play Role in Bone Size

New Haven, Conn. — Mice that do not make the protein CD200 have bigger bones, a finding that raises possibilities for treating osteoporosis, according to a report this week by a Yale School of Medicine researcher in Proceedings of the National Academy of Sciences.

“Osteoporosis is an insidious and devastating disease that results from the loss of bone mass, which leads to fractures of the spine, the hip, and the wrist,” said the senior author, Agnès Vignery, associate professor of orthopedics. “The identification of molecules that can be targeted to prevent bone loss is therefore essential.”

She said that a new avenue to prevent osteoporosis and possibly, to repair bone loss, was opened by the discovery of the CD200 protein that, together with its receptor CD200R, plays a role in bone resorption by osteoclasts, the cells that remodel bone.

Osteoclasts play a central role in the development of bone. Increases in their number and/or activity lead to diseases associated with generalized bone loss, such as in osteoporosis, and diseases related to localized bone loss, such as rheumatoid arthritis and periodontal disease.

Since fusion of macrophages is a key step in creating osteoclasts, the researchers examined this molecular mechanism using genome wide DNA microarray analysis and found the expression of CD200 at the onset of the fusion. They also found that mice deficient in CD200 had fewer osteoclasts and a higher bone density, and that the soluble recombinant form of CD200R that they engineered prevented the formation of osteoclasts.

“Together, our observations indicate that the CD200-CD200R axis plays a central role in the fusion of macrophages and the formation of osteoclasts,” the researchers said in their report.

Co-authors include Weiguo Cui, Esteban Cuartas, Juan Ke, Qing Zhang, and Halldor Einarsson, of Yale; Jonathon Sedgwick of Schering-Plough Biopharma, and Jun Li of Boehringher Ingelheim Pharmaceuticals Inc.

The study was supported with funds from the National Institutes of Health.