Estrogen inhibits Dlk1/FA1 production: A potential mechanism for estrogen effects on bone turnover

Authors

  • Basem M Abdallah,

    Corresponding author
    1. Endocrine Research Laboratory (KMEB), Department of Endocrinology and Metabolism, Odense University Hospital and University of Southern Denmark, Odense, Denmark
    2. Faculty of Science, Helwan University, Cairo, Egypt
    • Endocrine Research Laboratory (KMEB), Odense University Hospital, Medical Biotechnology Center, SDU, Winsloeparken 25, 1st floor, DK-5000 Odense C, Denmark.
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  • Anne-Christine Bay-Jensen,

    1. Department of Clinical Cell Biology, Center for Health Science Research and Education, University of Southern Denmark, Vejle Hospital, Vejle, Denmark
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  • Bhuma Srinivasan,

    1. Endocrine Research Unit, Mayo Clinic, Rochester, MN, USA
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  • Nadine C Tabassi,

    1. Department of Molecular Biomarkers, Synarc, Lyon, France
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  • Patrick Garnero,

    1. Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia
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  • Jean-Marie Delaissé,

    1. Department of Clinical Cell Biology, Center for Health Science Research and Education, University of Southern Denmark, Vejle Hospital, Vejle, Denmark
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  • Sundeep Khosla,

    1. Endocrine Research Unit, Mayo Clinic, Rochester, MN, USA
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  • Moustapha Kassem

    1. Endocrine Research Laboratory (KMEB), Department of Endocrinology and Metabolism, Odense University Hospital and University of Southern Denmark, Odense, Denmark
    2. Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia
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Abstract

We have recently identified delta-like 1/fetal antigen 1 (Dlk1/FA1) as a novel regulator of bone mass that functions to mediate bone loss under estrogen deficiency in mice. In this report, we investigated the effects of estrogen (E) deficiency and E replacement on serum (s) levels of Dlk1/FA1 (s-Dlk1FA1) and its correlation with bone turnover markers. s-Dlk1/FA1 and bone turnover markers (serum cross-linked C-telopeptide [s-CTX] and serum osteocalcin) were measured in two cohorts: a group of pre- and postmenopausal women (n = 100) and a group of postmenopausal women, where half had received estrogen-replacement therapy (ERT, n = 166). s-Dlk1/FA1 and s-CTX were elevated in postmenopausal E-deficient women compared with premenopausal E-replete women (both p < 0.001). s-Dlk1/FA1 was correlated with s-CTX (r = 0.30, p < 0.01). ERT in postmenopausal women decreased s-Dlk1/FA1, as well as s-CTX and s-osteoclacin (all p < .0001). Changes in s-Dlk1 were significantly correlated with those observed in s-CTX (r = 0.18, p < 0.05) and s-osteocalcin (r = 0.28, p < 0.001). In conclusion, s-Dlk1/FA1 is influenced by E-deficiency and is correlated with bone turnover. Increased levels of s-Dlk1/FA1 in postmenopausal women may be a mechanism mediating the effects of estrogen deficiency on bone turnover. © 2011 American Society for Bone and Mineral Research

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