Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1984 May;73(5):1277–1283. doi: 10.1172/JCI111329

Glucocorticoids modulate macrophage surface oligosaccharides and their bone binding activity.

Z Bar-Shavit, A J Kahn, L E Pegg, K R Stone, S L Teitelbaum
PMCID: PMC425148  PMID: 6715537

Abstract

The circumstantial evidence that indicates that glucocorticoids (GC) may stimulate osteoclastic resorption in vivo has recently found support in observations that demonstrate that these compounds effectively increase the activity of isolated resorptive cells (osteoclasts, macrophage polykaryons, and elicited macrophages [MO] ) in vitro. Data are presented here that indicate that this stimulation by GC is due to an enhancement of the initial stage of the resorption process, the attachment of cells to bone, and that this is caused by alterations of cell surface oligosaccharides. Specifically, dexamethasone and cortisol enhance by 80% the attachment of MO to bone surfaces in a dose dependent manner but do not alter or reduce the binding of these cells to other surfaces (plastic, collagen, and hydroxyapatite crystals). The effect of GC on cell-bone attachment is blocked by the glycosylation inhibitor, tunicamycin, and the glycosylation modifier, swainsonine; this demonstrates that asparagine-linked oligosaccharides are involved in the stimulatory process. Flow cytometric analysis of GC-treated cells using a panel of fluoresceinated lectins confirms this by indicating a selective, enhanced exposure of plasma membrane-associated N-acetylglucosamine and N-acetylgalactosamine residues, sugars we have previously shown to be pivotal in MO-bone binding. Finally, progesterone, a known GC antagonist, blocks GC-stimulated resorption, macrophage-bone binding, and membrane oligosaccharide modification, presumably by competing for the GC receptor. Progesterone alone alters none of these processes. Thus, GC stimulates the resorptive activity of macrophages by enhancing the initial events in the degradative process (cell-bone binding) and does so, apparently, via receptor-mediator alteration of cell surface glycoproteins.

Full text

PDF
1277

Images in this article

1279Image
on p.1279
1280Image
on p.1280

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bar-Shavit Z., Kahn A. J., Teitelbaum S. L. Defective binding of macrophages to bone in rodent osteomalacia and vitamin D deficiency. In vitro evidence for a cellular defect and altered saccharides in the bone matrix. J Clin Invest. 1983 Aug;72(2):526–534. doi: 10.1172/JCI111000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bar-Shavit Z., Teitelbaum S. L., Kahn A. J. Saccharides mediate the attachment of rat macrophages to bone in vitro. J Clin Invest. 1983 Aug;72(2):516–525. doi: 10.1172/JCI110999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Birkenhäger J. C., van der Heul R. O., Smeenk D., van der Sluys Veer J., van Seters A. P. Bone changes associated with glucocorticoid excess. Proc R Soc Med. 1967 Nov 1;60(11 Pt 1):1134–1136. doi: 10.1177/003591576706011P131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. Cupps T. R., Fauci A. S. Corticosteroid-mediated immunoregulation in man. Immunol Rev. 1982;65:133–155. doi: 10.1111/j.1600-065x.1982.tb00431.x. [DOI] [PubMed] [Google Scholar]
  6. Dorling P. R., Huxtable C. R., Colegate S. M. Inhibition of lysosomal alpha-mannosidase by swainsonine, an indolizidine alkaloid isolated from Swainsona canescens. Biochem J. 1980 Nov 1;191(2):649–651. doi: 10.1042/bj1910649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Duval D., Durant S., Homo-Delarche F. Non-genomic effects of steroids. Interactions of steroid molecules with membrane structures and functions. Biochim Biophys Acta. 1983 Aug 11;737(3-4):409–442. doi: 10.1016/0304-4157(83)90008-4. [DOI] [PubMed] [Google Scholar]
  8. Epker B. N. Studies on bone turnover and balance in the rabbit. I. Effects of hydrocortisone. Clin Orthop Relat Res. 1970 Sep-Oct;72:315–326. [PubMed] [Google Scholar]
  9. Goldman R., Bar-Shavit Z. Dual effect of normal and stimulated macrophages and their conditioned media on target cell proliferation. J Natl Cancer Inst. 1979 Oct;63(4):1009–1016. [PubMed] [Google Scholar]
  10. Hahn T. J., Halstead L. R., Teitelbaum S. L., Hahn B. H. Altered mineral metabolism in glucocorticoid-induced osteopenia. Effect of 25-hydroxyvitamin D administration. J Clin Invest. 1979 Aug;64(2):655–665. doi: 10.1172/JCI109506. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Ishii Y., Shinoda M., Shikita M. Specificity of the suppressive action of glucocorticoids on the proliferation of monocyte/macrophages in the CSF-stimulated cultures of mouse bone marrow. Exp Hematol. 1983 Mar;11(3):178–186. [PubMed] [Google Scholar]
  12. Jee W. S., Blackwood E. L., Dockum N. L., Haslam R. K., Kincl F. A. Bio-assay of responses of growing bones to cortisol. Clin Orthop Relat Res. 1966 Nov-Dec;49:39–63. [PubMed] [Google Scholar]
  13. Kahn A. J., Malone J. D., Teitelbaum S. L. Osteoclast precursors, mononuclear phagocytes, and bone resorption. Trans Assoc Am Physicians. 1981;94:267–278. [PubMed] [Google Scholar]
  14. 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]
  15. Motomura S., Katsuno M., Kaneko S., Ibayashi H. The effect of hydrocortisone on the production and differentiation of granulocyte/macrophage progenitor cells in long-term bone marrow cultures. Exp Hematol. 1983 Jan;11(1):56–62. [PubMed] [Google Scholar]
  16. Pietras R. J., Szego C. M. Surface modifications evoked by estradiol and diethylstilbestrol in isolated endometrial cells: evidence from lectin probes and extracellular release of lysosomal protease. Endocrinology. 1975 Dec;97(6):1445–1454. doi: 10.1210/endo-97-6-1445. [DOI] [PubMed] [Google Scholar]
  17. Raisz L. G., Trummel C. L., Wener J. A., Simmons H. Effect of glucocorticoids on bone resorption in tissue culture. Endocrinology. 1972 Apr;90(4):961–967. doi: 10.1210/endo-90-4-961. [DOI] [PubMed] [Google Scholar]
  18. Ramachandran C. K., Hignite C. E., Gray S. L., Melnykovych G. Evidence for the stimulation of dolichol and mannolipid synthesis by glucocorticoids in HeLa cells. Biochem J. 1981 Jul 15;198(1):23–28. doi: 10.1042/bj1980023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Rinehart J. J., Wuest D., Ackerman G. A. Corticosteroid alteration of human monocyte to macrophage differentiation. J Immunol. 1982 Oct;129(4):1436–1440. [PubMed] [Google Scholar]
  20. Simmons D. J., Kunin A. S. Autoradiographic and biochemical investigations of the effect of cortisone on the bones of the rat. Clin Orthop Relat Res. 1967 Nov-Dec;55:201–215. [PubMed] [Google Scholar]
  21. Suda T., Testa N. G., Allen T. D., Onions D., Jarrett O. Effect of hydrocortisone on osteoclasts generated in cat bone marrow cultures. Calcif Tissue Int. 1983;35(1):82–86. doi: 10.1007/BF02405011. [DOI] [PubMed] [Google Scholar]
  22. Teitelbaum S. L., Malone J. D., Kahn A. J. Glucocorticoid enhancement of bone resorption by rat peritoneal macrophages in vitro. Endocrinology. 1981 Mar;108(3):795–799. doi: 10.1210/endo-108-3-795. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Thompson J., van Furth R. The effect of glucocorticosteroids on the kinetics of mononuclear phagocytes. J Exp Med. 1970 Mar 1;131(3):429–442. doi: 10.1084/jem.131.3.429. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Thompson J., van Furth R. The effect of glucocorticosteroids on the proliferation and kinetics of promonocytes and monocytes of the bone marrow. J Exp Med. 1973 Jan 1;137(1):10–21. doi: 10.1084/jem.137.1.10. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Tu S. H., Nordquist R. E., Griffin M. J. Membrane changes in HeLa cells grown with cortisol. Biochim Biophys Acta. 1972 Dec 1;290(1):92–109. doi: 10.1016/0005-2736(72)90055-7. [DOI] [PubMed] [Google Scholar]
  27. Werb Z. Biochemical actions of glucocorticoids on macrophages in culture. Specific inhibition of elastase, collagenase, and plasminogen activator secretion and effects on other metabolic functions. J Exp Med. 1978 Jun 1;147(6):1695–1712. doi: 10.1084/jem.147.6.1695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Werb Z., Foley R., Munck A. Glucocorticoid receptors and glucocorticoid-sensitive secretion of neutral proteinases in a macrophage line. J Immunol. 1978 Jul;121(1):115–121. [PubMed] [Google Scholar]
  29. Werb Z., Foley R., Munck A. Interaction of glucocorticoids with macrophages. Identification of glucocorticoid receptors in monocytes and macrophages. J Exp Med. 1978 Jun 1;147(6):1684–1694. doi: 10.1084/jem.147.6.1684. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES