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Per-1 is a specific clock gene regulated by parathyroid hormone (PTH) signaling in osteoblasts and is functional for the transcriptional events induced by PTH

Authors

  • Ryo Hanyu,

    1. Department of Molecular Pharmacology, Medical Research Institute Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-Ku, 113-8510 Tokyo, Japan
    2. Department of Orthopedics, Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, 113-8421 Tokyo, Japan
    3. Global Center of Excellence Program for the International Research Center for Molecular Science in Tooth and Bone Disease, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-Ku, 113-8510 Tokyo, Japan
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  • Tadayoshi Hayata,

    Corresponding author
    1. Department of Molecular Pharmacology, Medical Research Institute Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-Ku, 113-8510 Tokyo, Japan
    2. Global Center of Excellence Program for the International Research Center for Molecular Science in Tooth and Bone Disease, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-Ku, 113-8510 Tokyo, Japan
    • Deptartment of Molecular Pharmacology, Medical Research Institute Tokyo Medical and Dental University, 5-45, Yushima 1-Chome, Bunkyo-Ku, 113-5810 Tokyo, Japan.
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  • Masashi Nagao,

    1. Department of Molecular Pharmacology, Medical Research Institute Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-Ku, 113-8510 Tokyo, Japan
    2. Department of Orthopedics, Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, 113-8421 Tokyo, Japan
    3. Global Center of Excellence Program for the International Research Center for Molecular Science in Tooth and Bone Disease, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-Ku, 113-8510 Tokyo, Japan
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  • Yoshitomo Saita,

    1. Department of Orthopedics, Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, 113-8421 Tokyo, Japan
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  • Hiroaki Hemmi,

    1. Department of Molecular Pharmacology, Medical Research Institute Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-Ku, 113-8510 Tokyo, Japan
    2. Global Center of Excellence Program for the International Research Center for Molecular Science in Tooth and Bone Disease, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-Ku, 113-8510 Tokyo, Japan
    3. Medical Top Track Program, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, 101-0062 Tokyo, Japan
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  • Takuya Notomi,

    1. Department of Molecular Pharmacology, Medical Research Institute Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-Ku, 113-8510 Tokyo, Japan
    2. Global Center of Excellence Program for the International Research Center for Molecular Science in Tooth and Bone Disease, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-Ku, 113-8510 Tokyo, Japan
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  • Tetsuya Nakamoto,

    1. Department of Molecular Pharmacology, Medical Research Institute Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-Ku, 113-8510 Tokyo, Japan
    2. Global Center of Excellence Program for the International Research Center for Molecular Science in Tooth and Bone Disease, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-Ku, 113-8510 Tokyo, Japan
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  • Ernestina Schipani,

    1. Harvard School of Medicine, Boston,
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  • Henry Knonenbery,

    1. Harvard School of Medicine, Boston,
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  • Kazuo Kaneko,

    1. Department of Orthopedics, Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, 113-8421 Tokyo, Japan
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  • Hisashi Kurosawa,

    1. Department of Orthopedics, Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, 113-8421 Tokyo, Japan
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  • Yoichi Ezura,

    1. Department of Molecular Pharmacology, Medical Research Institute Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-Ku, 113-8510 Tokyo, Japan
    2. Global Center of Excellence Program for the International Research Center for Molecular Science in Tooth and Bone Disease, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-Ku, 113-8510 Tokyo, Japan
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  • Masaki Noda

    Corresponding author
    1. Department of Molecular Pharmacology, Medical Research Institute Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-Ku, 113-8510 Tokyo, Japan
    2. Global Center of Excellence Program for the International Research Center for Molecular Science in Tooth and Bone Disease, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-Ku, 113-8510 Tokyo, Japan
    3. Hard Tissue Genome Research Center, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-Ku, 113-8510 Tokyo, Japan
    4. Advanced Bone Joint Science Center, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-Ku, 113-8510 Tokyo, Japan
    • Deptartment of Molecular Pharmacology, Medical Research Institute Tokyo Medical and Dental University, 5-45, Yushima 1-Chome, Bunkyo-Ku, 113-5810 Tokyo, Japan.
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Abstract

Per-1 is one of the clock genes and is known to regulate various biological events including bone mass determination. Parathyroid hormone is anabolic to bone while the mechanism of its action is not fully understood. Here, we examined the role of PTH on Per-1 gene expression under osteoblast specific PTH signaling. Constitutively active PTH receptor (caPPR) expressed specifically in osteoblasts in transgenic mice activates Per-1 gene expression in bone. This is specific as expression of other clock gene Bmal-1 is not affected by caPPR over-expression. Per-1 is also expressed in osteoblastic cell line. Interestingly, Per-1 expression is required for PTH signaling-induced CRE dependent transcription. This is forming a positive feed back loop in the anabolic action of PTH signaling and Per-1 in bone. These data indicate that PTH singling in osteoblasts activates Per-1 gene expression in vivo in association with its anabolic action in bone at least in part through the regulation of transcriptional events. J. Cell. Biochem. 112: 433–438, 2011. © 2010 Wiley-Liss, Inc.

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