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Normal human osteoclasts formed from peripheral blood monocytes express PTH type 1 receptors and are stimulated by PTH in the absence of osteoblasts

Authors

  • David W. Dempster,

    Corresponding author
    1. Regional Bone Center, Helen Hayes Hospital, New York State Department of Health, West Haverstraw, New York
    2. Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, New York
    • Regional Bone Center, Route 9W, West Haverstraw, NY 10993.
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  • Christine E. Hughes-Begos,

    1. Regional Bone Center, Helen Hayes Hospital, New York State Department of Health, West Haverstraw, New York
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  • Katarina Plavetic-Chee,

    1. Regional Bone Center, Helen Hayes Hospital, New York State Department of Health, West Haverstraw, New York
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  • Andrea Brandao-Burch,

    1. Department of Anatomy and Developmental Biology, University College London, London, United Kingdom
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  • Felicia Cosman,

    1. Clinical Research Center, Helen Hayes Hospital, New York State Department of Health, West Haverstraw, New York
    2. Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York
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  • Jeri Nieves,

    1. Clinical Research Center, Helen Hayes Hospital, New York State Department of Health, West Haverstraw, New York
    2. Department of Epidemiology, College of Physicians and Surgeons, Columbia University, New York, New York
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  • Simon Neubort,

    1. Regional Bone Center, Helen Hayes Hospital, New York State Department of Health, West Haverstraw, New York
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  • Shi Shou Lu,

    1. Regional Bone Center, Helen Hayes Hospital, New York State Department of Health, West Haverstraw, New York
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  • Akiko Iida-Klein,

    1. Regional Bone Center, Helen Hayes Hospital, New York State Department of Health, West Haverstraw, New York
    2. Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, New York
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  • Tim Arnett,

    1. Department of Anatomy and Developmental Biology, University College London, London, United Kingdom
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  • Robert Lindsay

    1. Clinical Research Center, Helen Hayes Hospital, New York State Department of Health, West Haverstraw, New York
    2. Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York
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Abstract

The prevailing view for many years has been that osteoclasts do not express parathyroid hormone (PTH) receptors and that PTH's effects on osteoclasts are mediated indirectly via osteoblasts. However, several recent reports suggest that osteoclasts express PTH receptors. In this study, we tested the hypothesis that human osteoclasts formed in vitro express functional PTH type 1 receptors (PTH1R). Peripheral blood monocytes (PBMC) were cultured on bone slices or plastic culture dishes with human recombinant RANK ligand (RANKL) and recombinant human macrophage colony-stimulating factor (M-CSF) for 16–21 days. This resulted in a mixed population of mono- and multi-nucleated cells, all of which stained positively for the human calcitonin receptor. The cells actively resorbed bone, as assessed by release of C-terminal telopeptide of type I collagen and the formation of abundant resorption pits. We obtained evidence for the presence of PTH1R in these cells by four independent techniques. First, using immunocytochemistry, positive staining for PTH1R was observed in both mono- and multi-nucleated cells intimately associated with resorption cavities. Second, PTH1R protein expression was demonstrated by Western blot analysis. Third, the cells expressed PTH1R mRNA at 21 days and treatment with 10−7M hPTH (1–34) reduced PTH1R mRNA expression by 35%. Finally, bone resorption was reproducibly increased by two to threefold when PTH (1–34) was added to the cultures. These findings provide strong support for a direct stimulatory action of PTH on human osteoclasts mediated by PTH1R. This suggests a dual regulatory mechanism, whereby PTH acts both directly on osteoclasts and also, indirectly, via osteoblasts. © 2005 Wiley-Liss, Inc.

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