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Studies on the role of 24-hydroxylation of vitamin D in the mineralization of cartilage and bone of vitamin D-deficient rats

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To test the importance of 24-hydroxylation of vitamin D3 on bone mineralization, rat pups born to vitamin D-deficient females were given either 25-hydroxyvitamin D3 or 24,24-difluoro-25-hydroxyvitamin D3 for 16 days beginning at the time of weaning. Following such treatment analysis of blood samples revealed no detectable 24R,25-(OH)2D3 and 1,25-(OH)2D3 in the rats given the difluoro compound while revealing the expected 24,24-difluoro-25-hydroxyvitamin D3 and 24,24-difluoro-1,25-dihydroxyvitamin D3. The rats given 25-hydroxyvitamin D3 had the expected levels of 25-hydroxyvitamin D3, 24,25-dihydroxyvitamin D3, and 1,25-dihydroxyvitamin D3. Following sacrifice at day 17, postweaning bone mineralization and modeling were studied in long bones using histological methods. Bones taken from vitamin D-deficient rats at the beginning and end of the experimental period had lesions typical of rickets. These included wide growth plates, excessive amounts of osteoid, and metaphyseal fibrosis. Following treatment with either 25-hydroxyvitamin D3 or 24,24-difluoro-25-hydroxyvitamin D3, bone mineralization returned to normal. Growth plate widths and the amount of osteoid on bone surfaces were both substantially reduced and to a similar degree in both treatment groups. Normal cartilage core formation and trabecularization of the metaphyseal primary spongiosa were also restored to a similar degree in both groups. In effect, no difference was observed in any bone parameter studied between the 25-hydroxyvitamin D3- and the 24,24-difluoro-25-hydroxyvitamin D3-treated animals. These results provide strong evidence that 24-hydroxylation of the vitamin D molecule plays little or no role in the modeling and mineralization of bone.

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References

  1. DeLuca, H. F.: Vitamin D endocrine system. In O. Bodanski, A. L. Latner (eds.): Advances in Clinical Chemistry, pp. 125–174. Academic Press, London, 1977

    Google Scholar 

  2. DeLuca, H. F.: Vitamin D. In H. F. DeLuca (ed.): Handbook of Lipid Research, pp. 69–132. Plenum Press, New York, 1978

    Google Scholar 

  3. Drezner, M. K., Harrelson, J. M.: Newer knowledge of vitamin D and its metabolites in health and disease, Clin. Orthop. Rel. Res.139:206–231, 1979

    CAS  Google Scholar 

  4. Holick, M. F., Baxter, L. A., Schraufrogel, P. K., Tavela, T. E., DeLuca, H. F.: Metabolism and biological activity of 24,25-dihydroxyvitamin D3 in the chick, J. Biol. Chem.251:397–402, 1976

    CAS  PubMed  Google Scholar 

  5. Boyle, I. T., Gray, R. W., DeLuca, H. F.: Regulation by calcium of in vivo synthesis of 1,25-dihydroxycholecalciferol and 21,25-dihydroxycholecalciferol, Proc. Natl. Acad. Sci. U.S.A.68:2131–2134, 1971

    CAS  PubMed  Google Scholar 

  6. Garabedian, M., Holick, M. F., DeLuca, H. F., Boyle, I. T.: Control of 25-hydroxycholecalciferol metabolism by parathyroid glands, Proc. Natl. Acad. Sci. U.S.A.69:1673–1676, 1972

    CAS  PubMed  Google Scholar 

  7. Fraser, D. M., Kodicek, E.: Regulation of 25-hydroxycholecalciferol-1-hydroxylase activity in kidney by parathyroid hormone, Nature [New Biol.]241:163–166, 1973

    CAS  Google Scholar 

  8. Henry, H., Midgett, R., Norman, A.: Regulation of 25-hydroxyvitamin D3-1-hydroxylase in vivo, J. Biol. Chem.249:7584–7592, 1974

    CAS  PubMed  Google Scholar 

  9. Halloran, B. P., Barthell, E., DeLuca, H. F.: Vitamin D metabolism during pregnancy and lactation in the rat, Proc. Natl. Acad. Sci. U.S.A.76:5549–5553, 1979

    CAS  PubMed  Google Scholar 

  10. Frolik, C. A., DeLuca, H. F.: 1,25-Dihydroxycholecalciferol: The metabolite of vitamin D responsible for increased intestinal calcium transport, Arch. Biochem. Biophys.147:143–147, 1971

    Article  CAS  PubMed  Google Scholar 

  11. Boyle, I. T., Miravet, L., Gray, R. W., Holick, M. F., DeLuca, H. F.: The response of intestinal calcium transport to 25-hydroxy and 1,25-dihydroxyvitamin D in nephrectomized rats, Endocrinology90:605–608, 1972

    Article  CAS  PubMed  Google Scholar 

  12. Tanaka, Y., DeLuca, H. F.: Bone mineral mobilization activity of 1,25-dihydroxycholecalciferol, a metabolite of vitamin D, Arch. Biochem. Biophys.146:574–578, 1971

    Article  CAS  PubMed  Google Scholar 

  13. Holick, M. F., Garabedian, M., DeLuca, H. F.: 1,25-Dihydroxycholecalciferol: a potent stimulator of bone resorption in tissue culture, Science176:1146–1148, 1972

    CAS  PubMed  Google Scholar 

  14. Raisz, L. G., Trummel, C. L., Holick, H. F., DeLuca, H. F.: 1,25-Dihydroxycholecalciferol: a potent stimulator of bone resorption in tissue culture, Science175:768–769, 1972

    CAS  PubMed  Google Scholar 

  15. Tanaka, Y., DeLuca, H. F., Ikekawa, N., Morisaki, M., Koizumi, N.: Determination of stereochemical configuration of the 24-hydroxy group of 24,25-dihydroxyvitamin D3 and its biological importance, Arch. Biochem. Biophys.170:620–626, 1975

    Article  CAS  PubMed  Google Scholar 

  16. Boris, A., Hurley, J. F., Trmal, T.: Relative activities of some metabolites and analogs of cholecalciferol in stimulation of tibia ash weight in chicks otherwise deprived of vitamin D, J. Nutr.107:194–198, 1977

    CAS  PubMed  Google Scholar 

  17. Boyle, I. T., Omdahl, J. L., Gray, R. W., DeLuca, H. F.: The biological activity and metabolism of 24,25-dihydroxyvitamin D3, J. Biol. Chem.248:4174–4180, 1973

    CAS  PubMed  Google Scholar 

  18. Kanis, J. A., Heynen, G., Russell, R. G. G., Smith, R., Walton, R. J., Warner, G. T.: Biological effects of 24,25-dihydroxycholecalciferol in man. In A. W. Norman, K. Schaefer, J. W. Coburn, H. F. DeLuca, D. Fraser, H. Grigoleit, D. von Herrath (eds.): Vitamin D: Biochemical, Chemical and Clinical Aspects Related to Calcium Metabolism, pp. 793–795. Walter de Gruyter, Berlin, 1977

    Google Scholar 

  19. Rasmussen, H., Bordier, P.: Vitamin D and bone, Metab. Bone Dis. Rel. Res.1:7–13, 1978

    Article  CAS  Google Scholar 

  20. Ornoy, A., Goodwin, D., Noff, D., Edelstein, S.: 24,25-Dihydroxyvitamin D is a metabolite of vitamin D essential for bone formation, Nature276:517–519, 1978

    Article  CAS  PubMed  Google Scholar 

  21. Noff, D., Edelstein, S.: Vitamin D and its hydroxylated metabolites in the rat, Horm. Res.9:292–300, 1978

    Article  CAS  PubMed  Google Scholar 

  22. Lieberherr, M., Garabedian, M., Guillozo, H., Baily du Bois, M., Balsan, S.: Interaction of 24,25-dihydroxyvitamin D3 and parathyroid hormone on bone enzymes in vitro, Calcif. Tissue Int.27:47–52, 1979

    CAS  PubMed  Google Scholar 

  23. Henry, H. L., Norman, A. W.: Vitamin D: two dihydroxylated metabolites are required for normal chicken egg hatchability, Science201:835–837, 1978

    CAS  PubMed  Google Scholar 

  24. Kobayashi, Y., Taguchi, T., Terada, T., Oshida, J., Morisaki, M., Ikekawa, N.: Synthesis of 24,24-difluoro- and 24ζ-fluoro-25-hydroxyvitamin D3, Tetrahedron Lett.22:2023–2026, 1979

    Article  Google Scholar 

  25. Yamada, S., Ohmari, M., Takayama, H.: Synthesis of 24,24-difluoro-25-hydroxyvitamin D3, Tetrahedron Lett.21:1859–1862, 1979

    Article  Google Scholar 

  26. Tanaka, Y., DeLuca, H. F., Ikekawa, N.: A study of the physiologic significance of 24-hydroxylation of 25-hydroxyvitamin D. In A. W. Norman, K. Schaefer, D. v. Herrath, H.-G. Grigoleit, J. W. Coburn, H. F. DeLuca, E. B. Mawer, T. Suda (eds.): Vitamin D: Basic Research and Its Clinical Application, pp. 531–536. Walter de Gruyter, Berlin, 1979

    Google Scholar 

  27. Tanaka, Y., DeLuca, H. F., Kobayashi, Y., Taguchi, T., Ikekawa, N., Morisaki, M.: Biological activity of 24,24-difluoro-25-hydroxyvitamin D3, J. Biol. Chem.254:7163–7167, 1979

    CAS  PubMed  Google Scholar 

  28. Halloran, B. P., and DeLuca, H. F.: Effect of vitamin D deficiency on fertility and reproductive capacity in the female rat, J. Nutr.110:1573–1580, 1980

    CAS  PubMed  Google Scholar 

  29. LeBel, D., Poirier, G. G., Beaudoin, A. R.: A convenient method for the ATPase assay, Anal. Biochem.85:86–89, 1978

    Article  CAS  PubMed  Google Scholar 

  30. Suda, T., DeLuca, H. F., Tanaka, Y.: Biological activity of 25-hydroxyergocalciferol in rats, J. Nutr.100:1049–1052, 1970

    CAS  PubMed  Google Scholar 

  31. Shepard, R. M., Horst, R. L., Hamstra, A. J., DeLuca, H. F.: Determination of vitamin D and its metabolites in plasma from normal and anephric man, Biochem. J.182:55–69, 1979

    CAS  PubMed  Google Scholar 

  32. Tanaka, Y., DeLuca, H. F., Schnoes, H. K., Ikekawa, N., Kobayashi, Y.: 24,24-Difluoro-1,25-dihydroxyvitamin D3:in vitro production, isolation, and biological activity, Arch. Biochem. Biophys.199:473–478, 1980

    Article  CAS  PubMed  Google Scholar 

  33. McMannus, J. F. A., Mowry, R. W.: Staining methods, histologic and histochemical, p. 201. Paul B. Hoeber, Inc., New York, 1960

    Google Scholar 

  34. Humphrey, C. D., Pittman, F. E.: A simple methylene blue-azure II-basic fuchsin stain for epoxy embedded tissue sections, Stain Technol.49:9–12, 1974

    CAS  PubMed  Google Scholar 

  35. Kimmel, D. B., Jee, W. S. S.: A rapid plastic embedding technique for preparation of three micron thick sections of decalcified hard tissue, Stain Technol.50:83–86, 1975

    CAS  PubMed  Google Scholar 

  36. Schenk, R.: Basic stereological principles. In Z. F. G. Jaworski (ed.): Bone Morphometry, pp. 21–23. University of Ottawa Press, Ottawa

  37. Miller, S. C., Jee, W. S. S.: Ethane-1-hydroxy-1,1-diphosphonate (EHDP) effects on growth and modeling of the rat tibia, Calcif. Tissue Res.18:215–231, 1975

    CAS  PubMed  Google Scholar 

  38. Bliss, C. I.: Statistics in Biology, Vol. 1, pp. 243–247. McGraw-Hill, New York, 1967

    Google Scholar 

  39. Heidelberger, C., Griesbach, L., Montas, B. J., Mooren, D., Cruz, O.: Studies on fluorinated pyrimidines. II. Effects on transplanted tumors, Cancer Res.18:305–317, 1958

    CAS  PubMed  Google Scholar 

  40. Napoli, J. L., Fivizzani, M. A., Schnoes, H. K., DeLuca, H. F.: 1α-Hydroxy-25-fluorovitamin D3: a potent analogue of 1α,25-dihydroxyvitamin D3, Biochemistry17:2387–2392, 1978

    Article  CAS  PubMed  Google Scholar 

  41. Napoli, J. L., Mellon, W. S., Fivizzani, M. A., Schnoes, H. K., DeLuca, H. F.: Synthesis and biological activity of 24-hydroxy-25-fluorovitamin D3, J. Biol. Chem.254:2017–2022, 1979

    CAS  PubMed  Google Scholar 

  42. Tanaka, Y., DeLuca, H. F., Schnoes, H. K., Ikekawa, N., Kobayashi, Y.: 24,24-Difluoro-1,25-dihydroxyvitamin D3:in vitro production, isolation, and biological activity, Arch. Biochem. Biophys.199:473–478, 1980

    Article  CAS  PubMed  Google Scholar 

  43. Corvol, M. T., Dumontier, M. F., Garabedian, M., Rappaport, R.: Vitamin D and cartilage. II. Biological activity of 25-hydroxycholecalciferol and 24,25-and 1,25-dihydroxycholecalciferols on cultured growth plate chondrocytes, Endocrinology102:1269–1274, 1978

    CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Radiobiology, Department of Pharmacology, College of Medicine, University of Utah, 84112, Salt Lake City, Utah, USA

    S. C. Miller & W. S. S. Jee

  2. Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin-Madison, 53706, Madison, Wisconsin, USA

    B. P. Halloran & H. F. DeLuca

  3. Faculty of Pharmaceutical Sciences, Teikyo University, 199-91, Sagamiko, Kanagawa, Japan

    S. Yamada & H. Takayama

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  1. S. C. Miller
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  3. H. F. DeLuca
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  4. S. Yamada
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  5. H. Takayama
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  6. W. S. S. Jee
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Miller, S.C., Halloran, B.P., DeLuca, H.F. et al. Studies on the role of 24-hydroxylation of vitamin D in the mineralization of cartilage and bone of vitamin D-deficient rats. Calcif Tissue Int 33, 489–497 (1981). https://doi.org/10.1007/BF02409479

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