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Published in: Calcified Tissue International 3/2016

01-09-2016 | Original Research

Osterix and RUNX2 are Transcriptional Regulators of Sclerostin in Human Bone

Authors: Flor M. Pérez-Campo, Ana Santurtún, Carmen García-Ibarbia, María A. Pascual, Carmen Valero, Carlos Garcés, Carolina Sañudo, María T. Zarrabeitia, José A. Riancho

Published in: Calcified Tissue International | Issue 3/2016

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Abstract

Sclerostin, encoded by the SOST gene, works as an inhibitor of the Wnt pathway and therefore is an important regulator of bone homeostasis. Due to its potent action as an inhibitor of bone formation, blocking sclerostin activity is the purpose of recently developed anti-osteoporotic treatments. Two bone-specific transcription factors, RUNX2 and OSX, have been shown to interact and co-ordinately regulate the expression of bone-specific genes. Although it has been recently shown that sclerostin is targeted by OSX in mice, there is currently no information of whether this is also the case in human cells. We have identified SP-protein family and AML1 consensus binding sequences at the human SOST promoter and have shown that OSX, together with RUNX2, binds to a specific region close to the transcription start site. Furthermore, we show that OSX and RUNX2 activate SOST expression in a co-ordinated manner in vitro and that SOST expression levels show a significant positive correlation with OSX/RUNX2 expression levels in human bone. We also confirmed previous results showing an association of several SOST/RUNX2 polymorphisms with bone mineral density.
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Metadata
Title
Osterix and RUNX2 are Transcriptional Regulators of Sclerostin in Human Bone
Authors
Flor M. Pérez-Campo
Ana Santurtún
Carmen García-Ibarbia
María A. Pascual
Carmen Valero
Carlos Garcés
Carolina Sañudo
María T. Zarrabeitia
José A. Riancho
Publication date
01-09-2016
Publisher
Springer US
Published in
Calcified Tissue International / Issue 3/2016
Print ISSN: 0171-967X
Electronic ISSN: 1432-0827
DOI
https://doi.org/10.1007/s00223-016-0144-4

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