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. 1983 Oct;80(19):5907–5911. doi: 10.1073/pnas.80.19.5907

Induction of monocytic differentiation and bone resorption by 1,25-dihydroxyvitamin D3.

Z Bar-Shavit, S L Teitelbaum, P Reitsma, A Hall, L E Pegg, J Trial, A J Kahn
PMCID: PMC390185  PMID: 6577459

Abstract

1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] stimulates bone resorption in man and other vertebrates, in part, by increasing the number of osteoclasts, the principal resorbing cells of bone. Because osteoclasts are very likely derived from a member(s) of the mononuclear phagocyte family, we determined if 1,25(OH)2D3 promotes maturation of these cells by studying its effects on the human promyelocytic leukemia cell line HL-60. Of the vitamin D3 metabolites tested, only 1,25(OH)2D3, at 10(-10) to 10(-7) M, induces the differentiation of HL60 into mono- and multinucleated macrophage-like cells. Phenotypic change is evident within 24 hr and reaches a plateau between 72 and 96 hr of incubation. The changes are metabolite-specific and include (i) adherence to substrate, (ii) acquisition of the morphological features of mature monocytes, (iii) a 4- to 6-fold enhancement in lysozyme synthesis and secretion, (iv) increase in the fraction of alpha-naphthyl acetate esterase-positive cells from approximately 2% to 100% of the population, and (v) the acquisition of several monocyte-associated cell surface antigens. More importantly, treated HL-60 cells acquire the capacity to bind and degrade bone matrix, two of the essential, functional characteristics of osteoclasts and related bone-resorbing cells. These results, considered together with the reported action of 1,25(OH)2D3 on nontransformed mononuclear cells, are consistent with the view that vitamin D3 enhances bone resorption and osteoclastogenesis in vivo by promoting the differentiation of precursor cells.

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Selected References

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  1. Abe E., Miyaura C., Sakagami H., Takeda M., Konno K., Yamazaki T., Yoshiki S., Suda T. Differentiation of mouse myeloid leukemia cells induced by 1 alpha,25-dihydroxyvitamin D3. Proc Natl Acad Sci U S A. 1981 Aug;78(8):4990–4994. doi: 10.1073/pnas.78.8.4990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bar-Shavit Z., Noff D., Edelstein S., Meyer M., Shibolet S., Goldman R. 1,25-dihydroxyvitamin D3 and the regulation of macrophage function. Calcif Tissue Int. 1981;33(6):673–676. doi: 10.1007/BF02409507. [DOI] [PubMed] [Google Scholar]
  3. Berger A. E., Davis J. E., Cresswell P. A human leukocyte antigen identified by a monoclonal antibody. Hum Immunol. 1981 Nov;3(3):231–245. doi: 10.1016/0198-8859(81)90020-3. [DOI] [PubMed] [Google Scholar]
  4. Bikle D. D., Morrissey R. L., Zolock D. T., Rasmussen H. The intestinal response to vitamin D. Rev Physiol Biochem Pharmacol. 1981;89:63–142. doi: 10.1007/BFb0035265. [DOI] [PubMed] [Google Scholar]
  5. Burger E. H., Van der Meer J. W., van de Gevel J. S., Gribnau J. C., Thesingh G. W., van Furth R. In vitro formation of osteoclasts from long-term cultures of bone marrow mononuclear phagocytes. J Exp Med. 1982 Dec 1;156(6):1604–1614. doi: 10.1084/jem.156.6.1604. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gordon S., Todd J., Cohn Z. A. In vitro synthesis and secretion of lysozyme by mononuclear phagocytes. J Exp Med. 1974 May 1;139(5):1228–1248. doi: 10.1084/jem.139.5.1228. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hanjan S. N., Kearney J. F., Cooper M. D. A monoclonal antibody (MMA) that identifies a differentiation antigen on human myelomonocytic cells. Clin Immunol Immunopathol. 1982 May;23(2):172–188. doi: 10.1016/0090-1229(82)90106-4. [DOI] [PubMed] [Google Scholar]
  8. Holtrop M. E., Cox K. A., Clark M. B., Holick M. F., Anast C. S. 1,25-dihydroxycholecalciferol stimulates osteoclasts in rat bones in the absence of parathyroid hormone. Endocrinology. 1981 Jun;108(6):2293–2301. doi: 10.1210/endo-108-6-2293. [DOI] [PubMed] [Google Scholar]
  9. Honma Y., Hozumi M., Abe E., Konno K., Fukushima M., Hata S., Nishii Y., DeLuca H. F., Suda T. 1 alpha,25-Dihydroxyvitamin D3 and 1 alpha-hydroxyvitamin D3 prolong survival time of mice inoculated with myeloid leukemia cells. Proc Natl Acad Sci U S A. 1983 Jan;80(1):201–204. doi: 10.1073/pnas.80.1.201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kahn A. J., Stewart C. C., Teitelbaum S. L. Contact-mediated bone resorption by human monocytes in vitro. Science. 1978 Mar 3;199(4332):988–990. doi: 10.1126/science.622581. [DOI] [PubMed] [Google Scholar]
  11. Ko J. S., Bernard G. W. Osteoclast formation in vitro from bone marrow mononuclear cells in osteoclast-free bone. Am J Anat. 1981 Aug;161(4):415–425. doi: 10.1002/aja.1001610407. [DOI] [PubMed] [Google Scholar]
  12. Koren H. S., Anderson S. J., Larrick J. W. In vitro activation of a human macrophage-like cell line. Nature. 1979 May 24;279(5711):328–331. doi: 10.1038/279328a0. [DOI] [PubMed] [Google Scholar]
  13. LITWACK G. Photometric determination of lysozyme activity. Proc Soc Exp Biol Med. 1955 Jul;89(3):401–403. doi: 10.3181/00379727-89-21824. [DOI] [PubMed] [Google Scholar]
  14. Lampson L. A., Levy R. Two populations of Ia-like molecules on a human B cell line. J Immunol. 1980 Jul;125(1):293–299. [PubMed] [Google Scholar]
  15. Lotem J., Sachs L. Regulation of normal differentiation in mouse and human myeloid leukemic cells by phorbol esters and the mechanism of tumor promotion. Proc Natl Acad Sci U S A. 1979 Oct;76(10):5158–5162. doi: 10.1073/pnas.76.10.5158. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. McCarthy D. M., San Miguel J. F., Freake H. C., Green P. M., Zola H., Catovsky D., Goldman J. M. 1,25-dihydroxyvitamin D3 inhibits proliferation of human promyelocytic leukaemia (HL60) cells and induces monocyte-macrophage differentiation in HL60 and normal human bone marrow cells. Leuk Res. 1983;7(1):51–55. doi: 10.1016/0145-2126(83)90057-7. [DOI] [PubMed] [Google Scholar]
  17. Miyaura C., Abe E., Kuribayashi T., Tanaka H., Konno K., Nishii Y., Suda T. 1 alpha,25-Dihydroxyvitamin D3 induces differentiation of human myeloid leukemia cells. Biochem Biophys Res Commun. 1981 Oct 15;102(3):937–943. doi: 10.1016/0006-291x(81)91628-4. [DOI] [PubMed] [Google Scholar]
  18. Morahan P. S. Macrophage nomenclature: where are we going? J Reticuloendothel Soc. 1980 Feb;27(2):223–245. [PubMed] [Google Scholar]
  19. Raff H. V., Picker L. J., Stobo J. D. Macrophage heterogeneity in man. A subpopulation of HLA-DR-bearing macrophages required for antigen-induced T cell activation also contains stimulators for autologous-reactive T cells. J Exp Med. 1980 Sep 1;152(3):581–593. doi: 10.1084/jem.152.3.581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Raisz L. G., Kream B. E., Smith M. D., Simmons H. A. Comparison of the effects of vitamin D metabolites on collagen synthesis and resportion of fetal rat bone in organ culture. Calcif Tissue Int. 1980;32(2):135–138. doi: 10.1007/BF02408532. [DOI] [PubMed] [Google Scholar]
  21. Rovera G., O'Brien T. G., Diamond L. Induction of differentiation in human promyelocytic leukemia cells by tumor promoters. Science. 1979 May 25;204(4395):868–870. doi: 10.1126/science.286421. [DOI] [PubMed] [Google Scholar]
  22. Rovera G., Santoli D., Damsky C. Human promyelocytic leukemia cells in culture differentiate into macrophage-like cells when treated with a phorbol diester. Proc Natl Acad Sci U S A. 1979 Jun;76(6):2779–2783. doi: 10.1073/pnas.76.6.2779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Tanaka H., Abe E., Miyaura C., Kuribayashi T., Konno K., Nishii Y., Suda T. 1 alpha,25-Dihydroxycholecalciferol and a human myeloid leukaemia cell line (HL-60). Biochem J. 1982 Jun 15;204(3):713–719. doi: 10.1042/bj2040713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Teitelbaum S. L., Stewart C. C., Kahn A. J. Rodent peritoneal macrophages as bone resorbing cells. Calcif Tissue Int. 1979 Jul 3;27(3):255–261. doi: 10.1007/BF02441194. [DOI] [PubMed] [Google Scholar]
  25. Ugolini V., Nunez G., Smith R. G., Stastny P., Capra J. D. Initial characterization of monoclonal antibodies against human monocytes. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6764–6768. doi: 10.1073/pnas.77.11.6764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Weinberg J. B. Tumor cell killing by phorbol ester--differentiated human leukemia cells. Science. 1981 Aug 7;213(4508):655–657. doi: 10.1126/science.7196085. [DOI] [PubMed] [Google Scholar]

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