Public Release: 

Key regulator of bone cells linked to osteoporosis

Yale University

MicroCT analysis of bone from mice with (M+/M+) and without (M-/M-) IRAK-M.
Click here for a high resolution photograph.

New Haven, Conn. -- Scientists at the Yale School of Medicine identified a molecule in osteoclasts, IRAK-M, that is a key regulator of the loss of bone mass.

Osteoclasts are cells that play a major role in the development and remodeling of bone. They originate from the fusion of macrophages and are important mediators of the loss of bone mass that leads to osteoporosis

Osteoporosis is a serious problem worldwide: it is characterized by loss of bone density leading to fractures in response to relatively mild trauma. Other disorders of localized bone loss include rheumatoid arthritis and periodontal disease.

The research on osteoporosis, led by Associate Professor Agnès Vignery in the Department of Orthopedics and Rehabilitation, focused on IRAK-M (interleukin-1 receptor associated kinase M), an intracellular signaling molecule previously found only in macrophages and in circulating white blood cells. Their theory was that if IRAK-M is maintained as macrophages fuse to form osteoclasts, it would block later steps in the signal pathway and keep osteoclasts from growing out of control.

"IRAK-M appears to be a key signaling molecule in the prevention of bone loss," said Vignery. "In normal mice the level of IRAK-M in osteoclasts is high compared to what is found in macrophages -- and bones are well maintained. Mice that lack IRAK-M develop severe osteoporosis."

The study was done with male mice, and possible association between sex hormones and the expression of IRAK-M remain to be investigated, according to Vignery. "For now, IRAK-M looks like an exciting new target for treating or preventing the devastation of osteoporosis and other localized problems of bone loss,"


Yale collaborators were Hongmei Li, Esteban Cuartas, Weiguo Cui and Koichi S, Kobayashi and Howard Hughes Medical Institute Investigator Richard A. Flavell who developed the mice lacking IRAK-M. Other authors were Hua Zhu Ke and Todd Crawford at Pfizer and Yongwon Choi at the University of Pennsylvania. Funding was from the National Institute of Dental and Craniofacial Research at the National Institutes of Health.

Citation: J. Experimental Medicine (April 4, 2005)

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.