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Transient modulation of calcium and parathyroid hormone stimulates bone formation

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Abstract

Intermittent administration of parathyroid hormone can stimulate bone formation. Parathyroid hormone is a natural hormone that responds to serum calcium levels. In this study, we examined whether a transient increase and/or decrease in the serum calcium can stimulate bone formation. Using a mathematical model previously developed, we first predicted the effects of administration of parathyroid hormone, neutralizing parathyroid hormone antibody, calcium, and EGTA (calcium chelator) on the serum concentration of parathyroid hormone and calcium. The model predicted that intermittent injection of parathyroid hormone and ethylene glycol tetraacetic acid transiently elevated the serum parathyroid hormone, while that of parathyroid hormone antibody and calcium transiently reduced parathyroid hormone in the serum. In vitro analysis revealed that parathyroid hormone’s transient changes (both up and down) elevated activating transcription factor 4-mediated osteocalcin expression. In the mouse model of osteoporosis, both intermittent administration of calcium and ethylene glycol tetraacetic acid showed tendency to increase bone mineral density of the upper limb (ulna and humerus) and spine, but the effects varied in a region-specific manner. Collectively, the study herein supports a common bone response to administration of calcium and its chelator through their effects on parathyroid hormone.

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Acknowledgments

We thank Edward Berbari for bringing our attention to pupillary responses to light stimulation, and Wenxiao Xu for technical assistance in animal studies. This study was supported in part by the Japan Society for the Promotion of Science Core-to-Core Program, 23003.

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    Authors and Affiliations

    1. Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA

      Andy B. Chen

    2. Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, IN, USA

      Kazumasa Minami & Hiroki Yokota

    3. Department of Medical Physics & Engineering Osaka University Graduate School of Medicine Suita, Osaka, Japan

      Kazumasa Minami & Masahiko Koizumi

    4. Department of Public Health, Medical School, New University of Lisbon, Lisbon, Portugal

      João F. Raposo

    5. Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan

      Nariaki Matsuura

    6. REQIMTE, Department of Chemistry, New University of Lisbon, Lisbon, Portugal

      Hugo G. Ferreira

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    1. Andy B. Chen
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    Correspondence to Hiroki Yokota.

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    Andy B. Chen and Kazumasa Minami contributed equally to this work.

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    Chen, A.B., Minami, K., Raposo, J.F. et al. Transient modulation of calcium and parathyroid hormone stimulates bone formation. Endocrine 54, 232–240 (2016). https://doi.org/10.1007/s12020-016-1066-7

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    • DOI: https://doi.org/10.1007/s12020-016-1066-7

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