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Science 26 May 2006:
Vol. 312. no. 5777, pp. 1223 - 1227
DOI: 10.1126/science.1126313
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Reports

Regulation of Adult Bone Mass by the Zinc Finger Adapter Protein Schnurri-3

Dallas C. Jones,1* Marc N. Wein,1* Mohamed Oukka,2,4 Jochen G. Hofstaetter,3,5 Melvin J. Glimcher,3 Laurie H. Glimcher1,4{dagger}

Genetic mutations that disrupt osteoblast function can result in skeletal dysmorphogenesis or, more rarely, in increased postnatal bone formation. Here we show that Schnurri-3 (Shn3), a mammalian homolog of the Drosophila zinc finger adapter protein Shn, is an essential regulator of adult bone formation. Mice lacking Shn3 display adult-onset osteosclerosis with increased bone mass due to augmented osteoblast activity. Shn3 was found to control protein levels of Runx2, the principal transcriptional regulator of osteoblast differentiation, by promoting its degradation through recruitment of the E3 ubiquitin ligase WWP1 to Runx2. By this means, Runx2-mediated extracellular matrix mineralization was antagonized, revealing an essential role for Shn3 as a central regulator of postnatal bone mass.

1 Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
2 Center for Neurologic Diseases, Brigham and Women's Hospital, Cambridge, MA 02139, USA.
3 Laboratory for the Study of Skeletal Disorders and Rehabilitation, Department of Orthopaedic Surgery, Harvard Medical School and Children's Hospital, Boston, MA 02115, USA.
4 Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
5 Ludwig Boltzmann Institute of Osteology, Vienna, A-1120 Austria.

* These authors contributed equally to this work.

{dagger} To whom correspondences should be addressed. E-mail: lglimche{at}hsph.harvard.edu

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