Steroid receptor coactivator-1 can regulate osteoblastogenesis independently of estrogen. (15th June 2017)

• Record Type: Journal Article
• Authors: Watters, R.J.; Hartmaier, R.J.; Osmanbeyoglu, H.U.; Gillihan, R.M.; Rae, J.M.; Liao, L.; Chen, K.; Li, W.; Lu, X.; Oesterreich, S.
• Is Part Of: Molecular and cellular endocrinology. Volume 448(2017)
• Page Start: 21
• Page End: 27
• Publication Date: 2017-06-15
• Subjects: NCOA1 -- SRC-1 -- Estrogen receptor -- Bone; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2017.03.005
• Languages: English
• ISSNs: 0303-7207

Abstract

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. Highlights: ChIP-Seq and microarray show SRC-1 regulated genes not dependent on E2 signaling. SRC-1 regulates genes critical in osteoblast differentiation independent of ERα. SRC-1 affects bone formation by altering how osteoblasts secrete ALPL and OCN.