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Misplaced metamorphosis
Date:3/3/2009

PHILADELPHIA Researchers at the University of Pennsylvania School of Medicine and the University of Connecticut have pinpointed the source of immature cells that spur misplaced bone growth. Unexpectedly, the major repository of bone-forming cells originates in blood vessels deep within skeletal muscle and other connective tissues, not from muscle stem cells themselves. The work also shows that cells important in the inflammatory response to injury trigger skeleton-stimulating proteins to transform muscle tissue into bone.

Understanding this process has important implications for understanding the formation of bone not only in FOP, a rare disease in which patients' muscle cells literally metamorphose to bone, but also in many common disorders of misplaced bone growth such as that following head injury, athletic injury, and spinal cord injury. The findings were published this week in the Journal of Bone & Joint Surgery.

"We always knew that heterotopic, or misplaced, bone growth was supplied by a rich vasculature, but we never suspected that cells from the blood vessels, when triggered by cells from the immune system, could undergo a metamorphosis that becomes a second skeleton," says senior author Frederick S. Kaplan, M.D., Isaac & Rose Nassau Professor of Orthopaedic Molecular Medicine. "When these components interact pathologically, as in the rare disease FOP, devastating results occur. We want to fix that."

The researchers used genetically engineered mice with labeled immature, or progenitor, cells to trace specific cell lineages through the process of renegade bone formation, which is induced by skeleton-stimulating molecules called bone morphogenetic proteins (BMPs). The study has important implications for understanding the rare genetic disorder fibrodysplasia ossificans progressiva (FOP), a condition studied by the authors who care for most of the world's 700 patients with the condition.

In FOP, the body fo
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
214-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert  

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