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Effects of vitamin D-binding protein on bone resorption stimulated by 1,25 dihydroxyvitamin D3

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Summary

Vitamin D and its metabolites are tightly bound to the serum vitamin D-binding protein (DBP) and only the free hormone is considered to be physiologically active. On the other hand, DBP could interact with cell membranes and even favor its intracellular entry. The present study was undertaken to examine the effects of DBP on bone resorption stimulated by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. Forelimb bones from 19-day-old fetal rats were cultured for 5 days in the presence of purified human or rat serum albumin (hSAP or rSAP) and 1,25(OH)2D3, with or without human or rat DBP (hDBP or rDBP). Bone resorption was assessed by measuring the release of previously incorporated45Ca. We found that the resorptive response to 1,25(OH)2D3 was minimally altered by hDBP (5 μM). The minimal effects of hDBP on 1,25(OH)2D3 activity on rat bones might be explained by a 6-fold lower affinity of hDBP (1.1×107 M−1) than rDBP (5.9×107 M−1) for 1,25(OH)2D3 or by species differences in cellular recognition of DBP. In a homologous rat system, however, rDBP at low (0.5 μM) or physiological (5 μM) concentration significantly decreased 1,25(OH)2D3-induced bone resorption. These data therefore support the hypothesis that free rather than DBP-bound 1,25(OH)2D3 is physiologically important.

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References

  1. Reichel H, Koeffler HP, Norman AW (1989) The role of the vitamin D endocrine system in health and disease. N Engl J Med 320:980–991

    Article  PubMed  CAS  Google Scholar 

  2. Raisz LG, Trummel CL, Holick MF, DeLuca HF (1972) 1,25-Dihydroxycholecalciferol: a potent stimulator of bone resorption in tissue culture. Science 175:768–769

    Article  PubMed  CAS  Google Scholar 

  3. Raisz LG, Kream BE, Smith MD, Simmons HA (1980) Comparison of the effects of vitamin D metabolites on collagen synthesis and resorption in fetal rat bone in organ culture. Calcif Tissue Int 32:135–138

    Article  PubMed  CAS  Google Scholar 

  4. Raisz LG, Maina DM, Gworek SG, Dietrich JW, Canalis EM (1978) Hormonal control of bone collagen synthesis in vitro—inhibitory effect of 1-hydroxylated vitamin D metabolites. Endocrinology 102:731–735

    PubMed  CAS  Google Scholar 

  5. Rowe DW, Kream BE (1982) Regulation of collagen synthesis in fetal rat calvaria by 1,25-dihydroxyvitamin D3. J Biol Chem 257:8009–8015

    PubMed  CAS  Google Scholar 

  6. Bouillon R, Van Baelen H, Rombauts W, De Moor P (1976) Purification and characterization of the human serum binding protein for 25-hydroxyvitamin D (trans-calciferin): identity with group-specific component (Gc). Eur J Biochem 66:285–291

    Article  PubMed  CAS  Google Scholar 

  7. Haddad JG, Walgate J (1976) 25-Hydroxyvitamin D transport in human plasma. Isolation and partial characterization of calcifidiol-binding protein. J Biol Chem 251:4803–4809

    PubMed  CAS  Google Scholar 

  8. Imawari M, Kida K, Goodman DWS (1976) The transport of vitamin D and its 25-hydroxy metabolite in human plasma: isolation and partial characterization of vitamin D and 25-hydroxyvitamin D-binding protein. J Clin Invest 58:514–523

    PubMed  CAS  Google Scholar 

  9. Bouillon R, Van Baelen H (1981) Transport of vitamin D: significance of free and total concentrations of the vitamin D metabolites. Calcif Tissue Int 33:451–453

    Article  PubMed  CAS  Google Scholar 

  10. Bikle DD, Siiteri PK, Ryzen E, Haddad JG (1985) Serum protein binding of 1,25-dihydroxyvitamin D: a re-evaluation by direct measurement of free metabolite levels. J Clin Endocrinol Metab 61:969–975

    PubMed  CAS  Google Scholar 

  11. Pardridge WM (1981) Transport of protein-bound hormones into tissues in vivo. Endocrine Rev 2:103–123

    Article  CAS  Google Scholar 

  12. Bouillon R, Van Assche FA, Van Baelen H, Heyns W, De Moor P (1981) Influence of the vitamin D-binding protein on the serum concentration of 1,25-dihydroxyvitamin D3. Significance of the free 1,25-dihydroxyvitamin D3 concentration. J Clin Invest 67:589–596

    PubMed  CAS  Google Scholar 

  13. Kumar R, Cohen WR, Epstein FH (1980) Vitamin D and calcium hormones in pregnancy. N Engl J Med 302:1143–1145

    Article  PubMed  CAS  Google Scholar 

  14. Nyomba BL, Verhaeghe, J, Thomasset M, Lisens W, Bouillon R (1989) Bone mineral homeostasis in spontaneously diabetic BB rats. I. Abnormal vitamin D metabolism and impaired active intestinal calcium absorption. Endocrinology 124:565–572

    PubMed  CAS  Google Scholar 

  15. Petrini M, Emerson DL, Galbraith RM (1983) Linkage between surface immunoglobulin and the cytoskeleton of B lymphocytes may involve Gc protein. Nature 306:73–74

    Article  PubMed  CAS  Google Scholar 

  16. Rosner W, Khan MS, Romas NA, Hryb DJ (1986) Interactions of plasma steroid-binding proteins with cell membranes. In: Forest M, Pugeat M (eds) Binding proteins of steroid hormones. John Libbey Eurotext, p 567

  17. Bikle DD, Gee E, Halloran B, Haddad JG (1984) Free 1,25-dihydroxyvitamin D levels in serum from normal subjects, pregnant subjects and subjects with liver disease. J Clin Invest 74:1966–1971

    PubMed  CAS  Google Scholar 

  18. Vanham G, Van Baelen H, Tan BK, Bouillon R (1988) The effect of vitamin D analogs and of vitamin D-binding protein on lymphocyte proliferation. J Steroid Biochem 29:381–386

    Article  PubMed  CAS  Google Scholar 

  19. Bikle DD, Gee E (1989) Free and not total, 1,25-dihydroxyvitamin D regulates 25-hydroxyvitamin D metabolism by keratinocytes. Endocrinology 124:649–654

    PubMed  CAS  Google Scholar 

  20. Haddad JG, Jennigns AS, Aw TC (1988) Vitamin D uptake and metabolism by perfused rat liver: influences of carrier proteins. Endocrinology 123:498–504

    PubMed  CAS  Google Scholar 

  21. Van Baelen H, Bouillon R (1986) Purification of the serum vitamin D-binding protein (DBP) from different species. In: Forest M, Pugeat M (eds) Binding proteins of steroid hormones. John Libbey Eurotext, p 69

  22. Bouillon R, Van Baelen H, De Moor P (1976) The transport of vitamin D in the serum of primates. Biochem J 159:463–466

    PubMed  CAS  Google Scholar 

  23. Bouillon R, Van Baelen H, De Moor P (1980) Compartive study of the affinity of the serum vitamin D-binding protein. J Steroid Biochem 13:1029–1034

    Article  PubMed  CAS  Google Scholar 

  24. Raisz LG (1965) Bone resorption in tissue culture. Factors influencing the response to parathyroid hormone. J Clin Invest 44:103–116

    PubMed  CAS  Google Scholar 

  25. Van Baelen H, Bouillon R, De Moor P (1980) Vitamin D-binding protein (Gc-globulin) binds acting. J Biol Chem 255:2270–2272

    PubMed  Google Scholar 

  26. Bouillon R, Van Baelen H (1982) The transport of vitamin D: significance of free and total concentrations of vitamin D metabolites. In: Norman A, Schaefer K, Herrath D, Grigoleit H (eds) Vitamin D, chemical, biochemical and clinical endocrinology of calcium metabolism. W de Gruyter, Berlin, pp 1181–1186

    Google Scholar 

  27. Bouillon R, Van Kerkhove P, De Moor P (1976) Characteristics of the vitamin D-binding proteins in different species. Calcif Tissue Res (suppl) 21:172–176

    PubMed  Google Scholar 

  28. Price PA (1986) Vitamin K-dependent formation of bone Gla protein (osteocalcin) and its function. Vitam Horm 42:65–107

    Article  Google Scholar 

  29. Silver J, Berry E (1982) Vitamin D uptake by the perfused rat liver is determined by its transport protein. Min Electrol Metab 7:298–304

    CAS  Google Scholar 

  30. Reddy GS, Jones G, Kooh SW, Fraser D, DeLuca HF (1983) Stimulation of 24R,25-dihydroxyvitamin D3 synthesis by metabolites of vitamin D3. Am Physiol Soc E359–E364

  31. Crilly RG, Marshall DH, Horsman A, Nordin BEC, Bouillon R (1980) 1-Hydroxy D3 with and without oestrogen in the treatment of osteoporosis. In: DeLuca H, Frost H, Pac W, Johnston C Jr, Parfitt A (eds) Osteoporosis: recent advances in pathogenesis and treatment. University Park Press, Baltimore, pp 425–432

    Google Scholar 

  32. Peacock M, Selby PL, Francis RM, Taylor GA (1985) The action and biological significance of female and male sex steroids on plasma total and free 1,25(OH)2D, parathyroid hormone and calcitonin. In: Norman A, Schaefer K, Grigoleit H, Herrath D (eds) Vitamin D: chemical, biochemical and clinical update. 6th Workshop Vitamin D, Italy. W de Gruyter, Berlin, New York, pp 595–596

    Google Scholar 

  33. Aarskog D, Aksnes L, Markestad T, Rodland O (1983) Effect of estrogen on vitamin D metabolism in tall girls. J Clin Endocrinol Metab 57:1155–1158

    Article  PubMed  CAS  Google Scholar 

  34. Cheema C, Grant BF, Marcus R (1989) Effects of estrogen on circulating “free” and total 1,25-dihydroxyvitamin D and on the parathyroid-vitamin D axis in postmenopausal women. J Clin Invest 83:537–542

    PubMed  CAS  Google Scholar 

  35. Halloran BP, DeLuca HF (1980) Calcium transport in small intestine during pregnancy and lactation. Am J Physiol 239:E64-E68

    PubMed  CAS  Google Scholar 

  36. Ishida H, Cunningham NS, Henry HL, Norman AW (1988) The number of 1,25-dihydroxyvitamin D3 receptors is decreased in both intestine and kidney of genetically diabetic db/db mice. Endocrinology 122:2436–2443

    Article  PubMed  CAS  Google Scholar 

  37. Bouillon R, Nyomba B, Decleer W, Van Baelen H (1985) Vitamin D-binding protein and free 1,25-dihydroxyvitamin D in animals and clinical medicine. In: Norman A, Schaefer K, Grigoleit H, Herrath D (eds) Vitamin D, chemical, biochemical and clinical update. W de Gruyter, Berlin, pp 669–673

    Google Scholar 

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Authors and Affiliations

  1. Division of Endocrinology and Metabolism, Department of Medicine, University of Connecticut Health Center, 06032, Farmington, CT, USA

    Socorro Vargas &  Lawrence G. Raisz

  2. Laboratorium voor Experimentele Geneeskunde en Endocrinologie, Gasthuisberg, Katholieke Universiteit Leuven, B-3000, Leuven, Belgium

    Roger Bouillon & Hugo Van Baelen

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  1. Socorro Vargas
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  2. Roger Bouillon
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  3. Hugo Van Baelen
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  4. Lawrence G. Raisz
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Vargas, S., Bouillon, R., Van Baelen, H. et al. Effects of vitamin D-binding protein on bone resorption stimulated by 1,25 dihydroxyvitamin D3 . Calcif Tissue Int 47, 164–168 (1990). https://doi.org/10.1007/BF02555982

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  • DOI: https://doi.org/10.1007/BF02555982

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