Biphasic effect of calcitonin on tartrate-resistant acid phosphatase activity in isolated rat osteoclasts

Authors

  • S. Yumita,

    1. University of Melbourne, Department of Medicine, St. Vincent's Hospital, Fitzroy, Victoria, Australia 3065
    2. University of Western Australia, Department of Medicine, Fremantle Hospital, Fremantle, Western Australia 6160
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  • Professor G.C. Nicholson,

    Corresponding author
    1. Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Queen Elizabeth II Medical Centre, Nedlands, Western Australia 6009
    • Department of Medicine The University of Melbourne The Geelong Hospital Geelong, Australia 3220
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  • D.J. Rowe,

    1. Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Queen Elizabeth II Medical Centre, Nedlands, Western Australia 6009
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  • G.N. Kent,

    1. University of Melbourne, Department of Medicine, St. Vincent's Hospital, Fitzroy, Victoria, Australia 3065
    Current affiliation:
    1. 4Jouban Chou Yumoto Hospital, Machi, Iwaki, Japan 972
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  • T.J. Martin

    1. University of Melbourne, Department of Medicine, St. Vincent's Hospital, Fitzroy, Victoria, Australia 3065
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Abstract

Tartrate-resistant acid phosphatase (TRAP) has been implicated as being involved in osteoclastic bone resorption, and calcitonin (CT) is known to inhibit the resorptive process. This study investigates the kinetics of CT action on TRAP activity in isolated rat osteoclasts using both biochemical and quantitative cytochemical methods. The latter technique has been developed to detect very small changes in intracellular TRAP activity at the single-cell level. The biochemical study showed that 10−9 M salmon CT (sCT) decreased TRAP activity in medium throughout the experimental period; TRAP activity in the cells was increased during the first 2 h but subsequently declined and was decreased to a significant level at 6 h. TRAP activity in sCT-treated osteoclasts measured by the cytochemical method showed significant increases within the first hour. This response was dose dependent between 1016 and 10−11 M sCT with EC50 at 8 × 10−14 M. After 1 h, the initial increase in intracellular TRAP activity in CT-treated osteoclasts was followed by a decline to below control levels, reaching statistical significance at 9 h. Treatment with forskolin (10−5 M) showed a similar trend, suggesting that this response is mediated by cyclic AMP-regulated phosphorylation events. From these results, we conclude that CT has two actions on TRAP in isolated rat osteoclasts: the first to inhibit its release, the second to inhibit its synthesis and/or increase its degradation.

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