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Glucocorticoids Inhibit Diastrophic Dysplasia Sulfate Transporter Activity in Otosclerosis by Interleukin-6

Authors

  • Yutaka Imauchi MD,

    1. Department of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
    2. Inserm EMI-U 0112, Faculté Xavier Bichat, Université Paris, France
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  • Marc Lombès MD, PhD,

    1. Inserm U.693, Faculté de Médecine Paris-Sud, Université Paris, Le Kremlin Bicêtre, France
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  • Pascale Lainé BSc,

    1. Inserm EMI-U 0112, Faculté Xavier Bichat, Université Paris, France
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  • Olivier Sterkers MD, PhD,

    1. Inserm EMI-U 0112, Faculté Xavier Bichat, Université Paris, France
    2. AP-HP, Beaujon Hospital, Department of Otolaryngology, Head and Neck Surgery, Clichy, France.
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  • Evelyne Ferrary MD, PhD,

    1. Inserm EMI-U 0112, Faculté Xavier Bichat, Université Paris, France
    2. AP-HP, Beaujon Hospital, Department of Otolaryngology, Head and Neck Surgery, Clichy, France.
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  • Alexis Bozorg Grayeli MD, PhD

    Corresponding author
    1. Inserm EMI-U 0112, Faculté Xavier Bichat, Université Paris, France
    2. AP-HP, Beaujon Hospital, Department of Otolaryngology, Head and Neck Surgery, Clichy, France.
    • Alexis Bozorg Grayeli, MD, PhD, Inserm EMI-U 0112, Faculté Xavier Bichat, 16, rue Henri Huchard, BP 416, F-75870 Paris Cedex 18, France.
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Abstract

Hypothesis/Objective: Otosclerosis is a bone remodeling disorder localized to the otic capsule and associated with inflammation. In vitro, increased activity of the diastrophic dysplasia sulf/te transporter (DTDST), which is implicated in bone metabolism, has been reported. Because glucocorticoids modulate the bone turnover and inhibit inflammatory processes, we investigated the effect of dexamethasone (Dex) on interleukin-6 and DTDST in otosclerosis.

Study Design: The authors conducted a prospective, case–control study.

Materials and Methods: Primary cell cultures were obtained from stapes and external auditory canals in otosclerosis (n = 21) and control patients (n = 18). Assays with [3H]Dex evaluated specific binding sites in otosclerotic and control stapes. The effects of Dex (10−9 to 10−6 M) and RU486 (10−7 M), a glucocorticoid antagonist, were studied on DTDST activity by sulfate uptake. IL-6 secretion was measured in culture media before and after Dex (10−7 M, 24 hours). The effect of IL-6 (10−7 M, 24 hours) was assessed on DTDST activity in control stapes.

Results: The number of specific Dex-binding sites was similar in all stapedial cultures. Dex inhibited DTDST activity (19.4 ± 1.02 vs. 29.4 ± 3.94 pmol/μg prot/5 minutes) only in otosclerotic stapes. This effect was dose-dependent, antagonized by RU 486 and only observed 24 hours after Dex exposure. Interleukin (IL)-6 stimulated DTDST activity in normal stapes, whereas Dex inhibited IL-6 production only in otosclerotic stapes.

Conclusion: Dex inhibits the DTDST activity, at least in part, through a reduction of IL-6 secretion only in otosclerotic cells. This effect is mediated through the glucocorticoid receptors and may lead to the reduction of bone turnover.

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