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Effect of 24R,25-dihydroxyvitamin D3 on the formation and function of osteoclastic cells

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Summary

Previous reports demonstrated that the administration of large doses of 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] to animals with normal vitamin D supply causes an increase in bone volume with reduced bone resorption and decreased osteoclast number. The present study was undertaken to clarify if 24R,25(OH)2D3 has any inhibitory effect on the formation and function of osteoclasts. The effect of 24R,25(OH)2D3 on the formation of osteoclastic cells was examined by measuring the number of tartrate-resistant acid phosphatase-positive multinucleated cells (MNCs) formed from hemopoietic progenitor cells obtained from spleens of 5-fluorouracil-treated mice. Treatment with 1,25(OH)2D3 or parathyroid hormone fragment 1–34 [PTH(1–34)] stimulated osteoclast-like MNC formation in a dose-dependent manner. Addition of 24R,25(OH)2D3 alone showed a weak stimulatory effect on MNC formation at 10-6 M, which appeared to be due to its binding to 1,25(OH)2D3 receptors. In contrast, when 24R,25(OH)2D3 was added together with 1,25(OH)2D3 or PTH(1–34), it inhibited osteoclast-like MNC formation stimulated by these hormones. A significant inhibition of MNC formation was observed with 10-7M 24R,25(OH)2D3, and the stimulatory effect of 1,25(OH)2D3 or PTH(1–34) was almost completely eliminated with 10-6 M 24R,25(OH)2D3. Neither 24S,25(OH)2D3 nor 25(OH)D3 exhibited a similar inhibitory effect. The effect of 24R,25(OH)2D3 on the resorptive function of osteoclasts was examined by measuring the formation of resorption pits by mouse bone cells on dentine slices. Treatment with 24R,25(OH)2D3 also inhibited the resorption pit formation stimulated by 1,25(OH)2D3 or PTH(1–34) with similar dose response. These results demonstrate that 24R,25(OH)2D3 has a specific inhibitory effect on the formation and function of osteoclastic cells stimulated by 1,25(OH)2D3 or PTH, and suggest that these effects of 24R,25(OH)2D3 may play role in the regulation of bone metabolism by modulating the actions of osteotropic hormones on osteoclastic bone resorption.

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Authors and Affiliations

  1. Fourth Department of Internal Medicine, University of Tokyo School of Medicine, 3-28-6 Mejirodai, Bunkyo-ku, 112, Tokyo, Japan

    Hideyuki Yamato, Ryo Okazaki, Tomoe Ishii, Etsuro Ogata & Toshio Matsumoto

  2. Biomedical Research Laboratories, Kureha Chemical Co, Shinjuku-ku, 169, Tokyo, Japan

    Keiko Akaogi & Nobuyuki Taniguchi

  3. Department of Oral Anatomy, Meikai University School of Dentistry, 350-02, Sakado, Saitama, Japan

    Takuya Sato & Masayoshi Kumegawa

Authors
  1. Hideyuki Yamato
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  2. Ryo Okazaki
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  3. Tomoe Ishii
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  4. Etsuro Ogata
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  5. Takuya Sato
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  6. Masayoshi Kumegawa
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  7. Keiko Akaogi
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  8. Nobuyuki Taniguchi
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  9. Toshio Matsumoto
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Yamato, H., Okazaki, R., Ishii, T. et al. Effect of 24R,25-dihydroxyvitamin D3 on the formation and function of osteoclastic cells. Calcif Tissue Int 52, 255–260 (1993). https://doi.org/10.1007/BF00298729

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  • DOI: https://doi.org/10.1007/BF00298729

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