PMID- 28286232 OWN - NLM STAT- MEDLINE DCOM- 20171121 LR - 20211015 IS - 1872-8057 (Electronic) IS - 0303-7207 (Linking) VI - 448 DP - 2017 Jun 15 TI - Steroid receptor coactivator-1 can regulate osteoblastogenesis independently of estrogen. PG - 21-27 LID - S0303-7207(17)30173-9 [pii] LID - 10.1016/j.mce.2017.03.005 [doi] AB - 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. CI - Copyright (c) 2017 Elsevier B.V. All rights reserved. FAU - Watters, R J AU - Watters RJ AD - 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. FAU - Hartmaier, R J AU - Hartmaier RJ AD - 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. FAU - Osmanbeyoglu, H U AU - Osmanbeyoglu HU AD - Computational Biology Program, Memorial Sloan Kettering Cancer Center, New York, USA. FAU - Gillihan, R M AU - Gillihan RM AD - Department of Dermatology, University of Florida, Gainesville, FL, USA. FAU - Rae, J M AU - Rae JM AD - Department of Pharmacology, University of Michigan, Ann Arbor, MI, USA. FAU - Liao, L AU - Liao L AD - Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, TX, USA. FAU - Chen, K AU - Chen K AD - Institute for Academic Medicine & Department of Cardiovascular Sciences, The Methodist Hospital Research Institute, Houston, TX 77030, USA. FAU - Li, W AU - Li W AD - Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA. FAU - Lu, X AU - Lu X AD - Department of Biomedical Informatics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. FAU - Oesterreich, S AU - Oesterreich S AD - 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. LA - eng GR - K99 CA207871/CA/NCI NIH HHS/United States GR - R01 GM099143/GM/NIGMS NIH HHS/United States GR - R21 DK082825/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20170307 PL - Ireland TA - Mol Cell Endocrinol JT - Molecular and cellular endocrinology JID - 7500844 RN - 0 (Estrogens) RN - EC 2.3.1.48 (Nuclear Receptor Coactivator 1) RN - EC 3.1.3.1 (Alkaline Phosphatase) SB - IM MH - Alkaline Phosphatase/metabolism MH - Animals MH - Bone Density/drug effects MH - Cell Differentiation/drug effects MH - Cell Line, Tumor MH - Estrogens/*pharmacology MH - Humans MH - Mice, Knockout MH - Nuclear Receptor Coactivator 1/*metabolism MH - Osteoblasts/cytology/drug effects/*metabolism MH - *Osteogenesis OTO - NOTNLM OT - Bone OT - Estrogen receptor OT - NCOA1 OT - SRC-1 EDAT- 2017/03/14 06:00 MHDA- 2017/11/29 06:00 CRDT- 2017/03/14 06:00 PHST- 2016/09/02 00:00 [received] PHST- 2017/03/04 00:00 [revised] PHST- 2017/03/04 00:00 [accepted] PHST- 2017/03/14 06:00 [pubmed] PHST- 2017/11/29 06:00 [medline] PHST- 2017/03/14 06:00 [entrez] AID - S0303-7207(17)30173-9 [pii] AID - 10.1016/j.mce.2017.03.005 [doi] PST - ppublish SO - Mol Cell Endocrinol. 2017 Jun 15;448:21-27. doi: 10.1016/j.mce.2017.03.005. Epub 2017 Mar 7.