Changes in dietary protein may override inherited skeletal abnormalities

Eating a diet with either high or low amounts of protein may override certain inherited developmental malformations of the skeleton, according to a new report in the December issue of the journal Cell Metabolism, published by Cell Press. Such so-called skeletal dysplasiae include more than 200 disorders of bone growth that lead to skeletal disproportions.

A study of mice led by Gerard Karsenty of Columbia University now uncovers new details of the molecular machinery that governs bone formation. Specifically, the researchers found that loss of a gene that is mutated in patients with a condition called neurofibromatosis (NF) type I causes an abnormal increase in activity of genes responsible for manufacturing bone.

The researchers also found a more general link between dietary amino acidsthe building blocks of proteinsand normal bone development. That result raised the possibility that changes in nutrition may, in some cases, offer a simple treatment for skeletal dysplasiae, according to the researchers, who conducted the work primarily at Baylor College of Medicine.

These results not only provide a molecular basis for NF skeletal manifestations, Karsenty said, but also identify a hitherto unanticipated connection between amino acid intake and skeletal development.

Neurofibromatosis type I, a disease which affects an estimated 1 in 3000 to 4000 people in the United States, is caused by loss of function of a gene encoding neurofibromin (NF1). In addition to well-described tumors of the nervous system, the condition in patients often includes skeletal abnormalities that have not been well understood, the researchers said.

As a result of the paucity of molecular knowledge of how neurofibromin affects bone biology, the only available treatment for these often debilitating manifestations remains surgery, Karsenty said.

To further elucidate NF1s skeletal role, Karsentys team generated mice that lacked the gen

Contact: Heidi Hardman
Cell Press

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