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Publication : Steroid receptor coactivator-1 can regulate osteoblastogenesis independently of estrogen.

First Author  Watters RJ Year  2017
Journal  Mol Cell Endocrinol Volume  448
Pages  21-27 PubMed ID  28286232
Mgi Jnum  J:251211 Mgi Id  MGI:6104101
Doi  10.1016/j.mce.2017.03.005 Citation  Watters RJ, et al. (2017) Steroid receptor coactivator-1 can regulate osteoblastogenesis independently of estrogen. Mol Cell Endocrinol 448:21-27
abstractText  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-ERalpha 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.
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