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; K Chen; W Li; X Lu; S Oesterreich

doi:10.1016/j.mce.2017.03.005

Steroid receptor coactivator-1 can regulate osteoblastogenesis independently of estrogen

Mol Cell Endocrinol. 2017 Jun 15:448:21-27. doi: 10.1016/j.mce.2017.03.005. Epub 2017 Mar 7.

Authors

R J Watters¹, R J Hartmaier², H U Osmanbeyoglu³, R M Gillihan⁴, J M Rae⁵, L Liao⁶, K Chen⁷, W Li⁸, X Lu⁹, S Oesterreich²

Affiliations

¹ Women's Cancer Research Center, University of Pittsburgh Cancer Institute, Magee Womens Research Institute, Pittsburgh, PA, USA; Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address: rjw63@pitt.edu.
² Women's Cancer Research Center, University of Pittsburgh Cancer Institute, Magee Womens Research Institute, Pittsburgh, PA, USA; Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
³ Computational Biology Program, Memorial Sloan Kettering Cancer Center, New York, USA.
⁴ Department of Dermatology, University of Florida, Gainesville, FL, USA.
⁵ Department of Pharmacology, University of Michigan, Ann Arbor, MI, USA.
⁶ Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
⁷ Institute for Academic Medicine & Department of Cardiovascular Sciences, The Methodist Hospital Research Institute, Houston, TX 77030, USA.
⁸ Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA.
⁹ Department of Biomedical Informatics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

PMID: 28286232
DOI: 10.1016/j.mce.2017.03.005

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.

Keywords: Bone; Estrogen receptor; NCOA1; SRC-1.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Alkaline Phosphatase / metabolism
Animals
Bone Density / drug effects
Cell Differentiation / drug effects
Cell Line, Tumor
Estrogens / pharmacology*
Humans
Mice, Knockout
Nuclear Receptor Coactivator 1 / metabolism*
Osteoblasts / cytology
Osteoblasts / drug effects
Osteoblasts / metabolism*
Osteogenesis*

Substances

Estrogens
Nuclear Receptor Coactivator 1
Alkaline Phosphatase

Abstract

Publication types

MeSH terms

Substances

Grants and funding