title: Osteopotentia regulates osteoblast maturation, bone formation, and skeletal integrity in mice.
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.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA. sohaskey@berkeley.edu
authors.forename: Michael L
authors.initials: ML
authors.lastname: Sohaskey
authors.forename: Yebin
authors.initials: Y
authors.lastname: Jiang
authors.forename: Jenny J
authors.initials: JJ
authors.lastname: Zhao
authors.forename: Andreas
authors.initials: A
authors.lastname: Mohr
authors.forename: Frank
authors.initials: F
authors.lastname: Roemer
authors.forename: Richard M
authors.initials: RM
authors.lastname: Harland
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D010012:Osteogenesis / Q000502:physiology*
chemical_list: D008565:Membrane Proteins; C550250:osteopotentia protein, mouse