期刊
MOLECULAR AND CELLULAR ENDOCRINOLOGY
卷 448, 期 C, 页码 21-27出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2017.03.005
关键词
NCOA1; SRC-1; Estrogen receptor; Bone
资金
- NIGMS [5R01GM099143-04]
- NIDDK [7R21DK082825-02]
- Department of Defense [BC123242]
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 U20S-ER alpha. 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. (C) 2017 Elsevier B.V. All rights reserved.
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