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Published online 7 March 2005. doi:10.1083/jcb.200408013
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 168, Number 6, 899-910
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Article

The high mobility group transcription factor Sox8 is a negative regulator of osteoblast differentiation



Katy Schmidt1, Thorsten Schinke2,3, Michael Haberland2,3, Matthias Priemel2,3, Arndt F. Schilling2,3, Cordula Mueldner2,3, Johannes M. Rueger2,3, Elisabeth Sock1, Michael Wegner1, and Michael Amling2,3

1 Institute of Biochemistry, Friedrich-Alexander-University, Erlangen-Nürnberg, Erlangen 91054, Germany
2 Department of Trauma, Hand and Reconstructive Surgery
3 Experimental Trauma Surgery and Skeletal Biology, Center for Biomechanics, Hamburg University School of Medicine, Hamburg 20246, Germany

Correspondence to M. Amling: amling{at}uke.uni-hamburg.de

Bone remodeling is an important physiologic process that is required to maintain a constant bone mass. This is achieved through a balanced activity of bone-resorbing osteoclasts and bone-forming osteoblasts. In this study, we identify the high mobility group transcription factor Sox8 as a physiologic regulator of bone formation. Sox8-deficient mice display a low bone mass phenotype that is caused by a precocious osteoblast differentiation. Accordingly, primary osteoblasts derived from these mice show an accelerated mineralization ex vivo and a premature expression of osteoblast differentiation markers. To confirm the function of Sox8 as a negative regulator of osteoblast differentiation we generated transgenic mice that express Sox8 under the control of an osteoblast-specific Col1a1 promoter fragment. These mice display a severely impaired bone formation that can be explained by a strongly reduced expression of runt-related transcription factor 2, a gene encoding a transcription factor required for osteoblast differentiation. Together, these data demonstrate a novel function of Sox8, whose tightly controlled expression is critical for bone formation.

K. Schmidt and T. Schinke contributed equally to this paper.

Abbreviations used in this paper: Bsp, bone sialoprotein; Lrp5, low density lipoprotein receptor-related protein 5; Osc, osteocalcin; Osx, osterix; Phex, phosphate-regulating gene with homologies to endopeptidases located on the X-chromosome; Runx2, runt-related transcription factor 2; Tnsalp; tissue-nonspecific alkaline phosphatase.


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