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Osteopotentia regulates osteoblast maturation, bone formation, and skeletal integrity in mice

Michael L. Sohaskey, Yebin Jiang, Jenny J. Zhao, Andreas Mohr, Frank Roemer and Richard M. Harland
The Journal of Cell Biology
Vol. 189, No. 3 (MAY 3, 2010), pp. 511-525
Stable URL: http://www.jstor.org/stable/20698083
Page Count: 15
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Osteopotentia regulates osteoblast maturation, bone formation, and skeletal integrity in mice
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Abstract

During skeletal development and regeneration, bone-forming osteoblasts respond to high metabolic demand by active expansion of their rough endoplasmic reticulum (rER) and increased synthesis of type I collagen, the predominant bone matrix protein. However, the molecular mechanisms that orchestrate this response are not well understood. We show that insertional mutagenesis of the previously uncharacterized osteopotentia (Opt) gene disrupts osteoblast function and causes catastrophic defects in postnatal skeletal development. Opt encodes a widely expressed rER-localized integral membrane protein containing a conserved SUN (Sad1/Unc-84 homology) domain. Mice lacking Opt develop acute onset skeletal defects that include impaired bone formation and spontaneous fractures. These defects result in part from a cell-autonomous failure of osteoblast maturation and a posttranscriptional decline in type I collagen synthesis, which is concordant with minimal rER expansion. By identifying Opt as a crucial regulator of bone formation in the mouse, our results uncover a novel rER-mediated control point in osteoblast function and implicate human Opt as a candidate gene for brittle bone disorders.

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