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.