title: Steroid receptor coactivator-1 can regulate osteoblastogenesis independently of estrogen.
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.
authors.affiliation: 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.
authors.forename: R J
authors.initials: RJ
authors.lastname: Watters
authors.affiliation: 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.
authors.forename: R J
authors.initials: RJ
authors.lastname: Hartmaier
authors.affiliation: Computational Biology Program, Memorial Sloan Kettering Cancer Center, New York, USA.
authors.forename: H U
authors.initials: HU
authors.lastname: Osmanbeyoglu
authors.affiliation: Department of Dermatology, University of Florida, Gainesville, FL, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Gillihan
authors.affiliation: Department of Pharmacology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Rae
authors.affiliation: Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: L
authors.initials: L
authors.lastname: Liao
authors.affiliation: Institute for Academic Medicine & Department of Cardiovascular Sciences, The Methodist Hospital Research Institute, Houston, TX 77030, USA.
authors.forename: K
authors.initials: K
authors.lastname: Chen
authors.affiliation: Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA.
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Biomedical Informatics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: X
authors.initials: X
authors.lastname: Lu
authors.affiliation: 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.
authors.forename: S
authors.initials: S
authors.lastname: Oesterreich
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D004967:Estrogens / Q000494:pharmacology*; D006801:Humans; D018345:Mice, Knockout; D056920:Nuclear Receptor Coactivator 1 / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010012:Osteogenesis
chemical_list: D004967:Estrogens; D056920:Nuclear Receptor Coactivator 1; D000469:Alkaline Phosphatase
keywords: Bone; Estrogen receptor; NCOA1; SRC-1