Role of BMPs in the regulation of sclerostin as revealed by an epigenetic modifier of human bone cells

Jesús Delgado-Calle, Jana Arozamena, Javier Pérez-López, Alfonso Bolado-Carrancio, Carolina Sañudo, Gloria Agudo, Rosa de la Vega, María A. Alonso, José Carlos Rodríguez-Rey, José A. Riancho

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Sclerostin, encoded by the SOST gene, is specifically expressed by osteocytes. However osteoblasts bear a heavily methylated SOST promoter and therefore do not express SOST. Thus, studying the regulation of human SOST is challenged by the absence of human osteocytic cell lines. Herein, we explore the feasibility of using the induction of SOST expression in osteoblasts by a demethylating agent to study the mechanisms underlying SOST transcription, and specifically, the influence of bone morphogenetic proteins (BMPs).Microarray analysis and quantitative PCR showed that AzadC up-regulated the expression of several BMPs, including BMP-2, BMP-4 and BMP-6, as well as several BMP downstream targets. Recombinant BMP-2 increased the transcriptional activity of the SOST promoter cloned into a reporter vector. Likewise, exposing cells transfected with the vector to AzadC also resulted in increased transcription. On the other hand, inhibition of the canonical BMP signaling blunted the effect of AzadC on SOST.These results show that the AzadC-induced demethylation of the SOST promoter in human osteoblastic cells may be a valuable tool to study the regulation of SOST expression. As a proof of concept, it allowed us to demonstrate that BMPs stimulate SOST expression by a mechanism involving BMPR1A receptors and downstream Smad-dependent pathways.

Original languageEnglish (US)
Pages (from-to)27-34
Number of pages8
JournalMolecular and Cellular Endocrinology
Volume369
Issue number1-2
DOIs
StatePublished - Apr 30 2013
Externally publishedYes

Keywords

  • BMPs
  • DNA methylation
  • Gene transcription
  • SOST

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Fingerprint Dive into the research topics of 'Role of BMPs in the regulation of sclerostin as revealed by an epigenetic modifier of human bone cells'. Together they form a unique fingerprint.

  • Cite this

    Delgado-Calle, J., Arozamena, J., Pérez-López, J., Bolado-Carrancio, A., Sañudo, C., Agudo, G., de la Vega, R., Alonso, M. A., Rodríguez-Rey, J. C., & Riancho, J. A. (2013). Role of BMPs in the regulation of sclerostin as revealed by an epigenetic modifier of human bone cells. Molecular and Cellular Endocrinology, 369(1-2), 27-34. https://doi.org/10.1016/j.mce.2013.02.002