Mice provide insight into bone metabolism disorders

St. Louis, August 4, 2002 -- Mice lacking a protein called SHIP (Src homology 2-containing inositol-5-phosphatase) have twice as many cells that breakdown bone as normal mice, according to a study led by Washington University School of Medicine in St. Louis. Consequently, the mice lose a significant amount of bone density and thickness. These results not only provide insight into diseases of bone metabolism such as osteoporosis, but the mouse strain used in the study also may be the first animal model of a rare genetic disease called juvenile Paget's disease (JPD).

"Our findings are important for understanding how bone forms and breaks down, and how those processes are disrupted in diseases like JPD," says F. Patrick Ross, Ph.D., research professor of pathology and immunology at the School of Medicine.

Ross led the study, which appears online in Nature Medicine on Aug. 5 and will be published in the September issue of the journal. The first authors were Sunao Takeshita, Ph.D., and Noriyuki Namba, Ph.D., both post-doctoral fellows in Ross' laboratory.

JPD, also known as hereditary hyperphosphatasia or hyperostosis corticalis deformans juvenilis, is a painful skeletal disease characterized by abnormally fast formation and breakdown of bone throughout the body that leads to debilitating fractures and deformities beginning soon after birth.

In healthy individuals, there is a careful balance between the number of osteoblasts (cells that create bone) and osteoclasts (cells that break down bone). But research suggests that people with JPD have more osteoclasts and that these cells are larger than normal, which creates a dangerous imbalance in bone turnover.

Researchers in Vancouver recently engineered a strain of mice lacking the gene for SHIP. The mice have abnormally high numbers of macrophages, a type of immune cell. Because macrophages can develop into osteoclasts, the Washington University team hypothesized that the mice lack

Contact: Gila Z. Reckess
Washington University School of Medicine

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