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Title

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

AuthorsFrutos, Cristina A. de; Dacquin, Romain; Vega, Sonia; Jurdic, Pierre; Machuca-Gayet, Irma; Nieto, M. Ángela CSIC ORCID
KeywordsMasa ósea
Snail
Desmineralización
Osteoblastos
Vitamina D
Runx2
Bone remodelling
Osteoblasts
Osteoclasts
Vitamin D receptor (VDR)
Issue Date5-Feb-2009
PublisherNature Publishing Group
CitationEMBO Journal 28(6): 686-696 (2009)
AbstractBone 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.
Description11 pages, 8 figures.-- PMID: 19197242 [PubMed].-- Supporting information available (Suppl. figures S1-S7 + Suppl. table I).
Publisher version (URL)http://dx.doi.org/10.1038/emboj.2009.23
URIhttp://hdl.handle.net/10261/10451
DOI10.1038/emboj.2009.23
ISSN0261-4189
Appears in Collections:(IN) Artículos




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