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  • The EMBO Journal (2009) 28, 686 - 696
  • doi:10.1038/emboj.2009.23

Published online: 5 February 2009

Snail1 controls bone mass by regulating Runx2 and VDR expression during osteoblast differentiationEMBO Open

Cristina A de Frutos1, Romain Dacquin2,a, Sonia Vega1,a, Pierre Jurdic2, Irma Machuca-Gayet2 and M Angela Nieto1

  1. Instituto de Neurociencias, CSIC-UMH, San Juan de Alicante, Spain
  2. Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, CNRS, INRA ENS Lyon +IFR 128, Biosciences Lyon-Gerland, Lyon, France

Correspondence to:

M Angela Nieto, Instituto de Neurociencias, CSIC-UMH, Avda. Ramón y Cajal s/n, San Juan de Alicante 03550, Spain. Tel.: +34 965 919243; Fax: +34 965 91 95 61; E-mail: anieto@umh.es

aThese authors contributed equally to this work

Received 19 September 2008; Accepted 13 January 2009

Bone undergoes continuous remodelling throughout adult life, and the equilibrium between bone formation by osteoblasts and bone resorption by osteoclasts defines the final bone mass. Here we show that Snail1 regulates this balance by controlling osteoblast differentiation. Snail1 is necessary for the early steps of osteoblast development, and it must be downregulated for their final differentiation. At the molecular level, Snail1 controls bone mass by repressing the transcription of both the osteoblast differentiation factor Runx2 and the vitamin D receptor (VDR) genes in osteoblasts. Sustained activation of Snail1 in transgenic mice provokes deficient osteoblast differentiation, which, together with the loss of vitamin D signalling in the bone, also impairs osteoclastogenesis. Indeed, the mineralisation of the bone matrix is severely affected, leading to hypocalcemia-independent osteomalacia. Our data show that the impact of Snail1 activity on the osteoblast population regulates the course of bone cells differentiation and ensures normal bone remodelling.

  • Keywords:

    • bone remodelling,
    • osteoblasts,
    • osteoclasts,
    • Runx2,
    • snail,
    • VDR

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The EMBO Journal is published by Nature Publishing Group on behalf of European Molecular Biology Organization