Steroid receptor coactivator-1 can regulate osteoblastogenesis independently of estrogen

R. J. Watters, R. J. Hartmaier, H. U. Osmanbeyoglu, R. M. Gillihan, J. M. Rae, L. Liao, Kaifu Chen, W. Li, X. Lu, S. Oesterreich

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Steroid receptor coactivator-1 (SRC-1), a well-studied coactivator of estrogen receptor (ER), is known to play an important and functional role in the development and maintenance of bone tissue. Previous reports suggest SRC-1 maintains bone mineral density primarily through its interaction with ER. Here we demonstrate that SRC-1 can also affect bone development independent of estrogen signaling as ovariectomized SRC-1 knockout (SRC-1 KO) mouse had decreased bone mineral density. To identify estrogen-independent SRC-1 target genes in osteoblastogenesis, we undertook an integrated analysis utilizing ChIP-Seq and mRNA microarray in transformed osteoblast-like U2OS-ERα cells. We identified critical osteoblast differentiation genes regulated by SRC-1, but not by estrogen including alkaline phosphatase and osteocalcin. Ex vivo primary culture of osteoblasts from SRC-1 wild-type and KO mice confirmed the role of SRC-1 in osteoblastogenesis, associated with altered ALPL levels. Together, these data indicate that SRC-1 can impact osteoblast function in an ER-independent manner.

Original languageEnglish (US)
Pages (from-to)21-27
Number of pages7
JournalMolecular and cellular endocrinology
Volume448
DOIs
StatePublished - Jun 15 2017

Keywords

  • Bone
  • Estrogen receptor
  • NCOA1
  • SRC-1

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

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