Interleukin-17: A New Bone Acting Cytokine In Vitro

Authors

  • Rutger L. Van Bezooijen,

    Corresponding author
    1. Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands
    • Address reprint requests to: Rutger L. van Bezooijen, Department of Endocrinology and Metabolic Diseases, Building 1, C4-R89, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands
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  • Hetty C. M. Farih-Sips,

    1. Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands
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  • Socrates E. Papapoulos,

    1. Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands
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  • Clemens W. G. M. Löwik

    1. Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands
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  • Presented in part at the 19th Annual Meeting of the American Society for Bone and Mineral Research, September 10–14, 1997, Cincinnati, OH, U.S.A. (J Bone Miner Res 12 (Suppl 1):S342) and the Second Joint Meeting of the American Society for Bone and Mineral Research and the International Bone and Mineral Society, December 1–6, 1998, San Francisco, CA, U.S.A. (Bone 23 (Suppl):S441).

Abstract

Interleukin-17 (IL-17) is a recently cloned cytokine that is exclusively produced by activated T cells, but its receptor has been found on several cells and tissues. Like other proinflammatory cytokines produced by activated T cells, IL-17 may affect osteoclastic resorption and thereby mediate bone destruction accompanying some inflammatory diseases. In the present study, we investigated whether osteogenic cells possess the receptor for IL-17 (IL-17R) and whether IL-17 affects osteoclastic resorption. We found that IL-17R mRNA is expressed both in mouse MC3T3-E1 osteoblastic cells and fetal mouse long bones, suggesting that osteogenic cells may be responsive to IL-17. In fetal mouse long bones, IL-17 had no effect on basal and IL-1β–stimulated osteoclastic bone resorption, but when given together with tumor necrosis factor-α (TNF-α) it increased bone resorption dose dependently in serum-free conditions. In addition, IL-17 increased TNF-α–induced IL-1α, IL-1β, and IL-6 mRNA expression in fetal mouse metatarsals and IL-1α and IL-6 mRNA expression in MC3T3-E1 cells. In conclusion, IL-17R mRNA was expressed by mouse osteoblastic cells and fetal mouse long bones, and IL-17 in combination with TNF-α, but not IL-1β, increased osteoclastic resorption in vitro. IL-17 may therefore affect bone metabolism in pathological conditions characterized by the presence of activated T cells and TNF-α production such as rheumatoid arthritis and loosening of bone implants.

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