Skip to main content
International Journal of Experimental Pathology logoLink to International Journal of Experimental Pathology
. 1995 Feb;76(1):37–42.

The role of 1,25-dihydroxycholecalciferol and prostaglandin E2 in the regulation of human osteoclastic bone resorption in vitro.

A M Flanagan 1, M D Stow 1, N Kendall 1, W Brace 1
PMCID: PMC1997135  PMID: 7734338

Abstract

Prostaglandins increase human osteoclast generation in vivo whereas they have been shown to exert the opposite effect in vitro: the latter results are based on enumeration of osteoclast-like cells, whose nature is controversial. We have generated human osteoclasts in vitro as assessed by bone resorption, a function unique to the osteoclast, and analysed the role of prostaglandin E2 (PGE2) in osteoclast activity. Human bone marrow cells were cultured to form a mature stroma and then sedimented onto bone slices with or without a recharge of non-adherent bone marrow cells. Bone resorption was increased by 1,25-dihydroxycholecalciferol (1,25(OH)2D3) and PGE2 and inhibited by indomethacin: this inhibition was reversed by addition of PGE2. Our work supports the observation that PGE2 increases bone resorption in vivo and demonstrates the value of assessing osteoclast generation and activity in vitro using bone resorption.

Full text

PDF
37

Images in this article

Selected References

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

  1. Akatsu T., Takahashi N., Debari K., Morita I., Murota S., Nagata N., Takatani O., Suda T. Prostaglandins promote osteoclastlike cell formation by a mechanism involving cyclic adenosine 3',5'-monophosphate in mouse bone marrow cell cultures. J Bone Miner Res. 1989 Feb;4(1):29–35. doi: 10.1002/jbmr.5650040106. [DOI] [PubMed] [Google Scholar]
  2. Chambers T. J., Owens J. M., Hattersley G., Jat P. S., Noble M. D. Generation of osteoclast-inductive and osteoclastogenic cell lines from the H-2KbtsA58 transgenic mouse. Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5578–5582. doi: 10.1073/pnas.90.12.5578. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chambers T. J., Revell P. A., Fuller K., Athanasou N. A. Resorption of bone by isolated rabbit osteoclasts. J Cell Sci. 1984 Mar;66:383–399. doi: 10.1242/jcs.66.1.383. [DOI] [PubMed] [Google Scholar]
  4. Chenu C., Kurihara N., Mundy G. R., Roodman G. D. Prostaglandin E2 inhibits formation of osteoclastlike cells in long-term human marrow cultures but is not a mediator of the inhibitory effects of transforming growth factor beta. J Bone Miner Res. 1990 Jul;5(7):677–681. doi: 10.1002/jbmr.5650050703. [DOI] [PubMed] [Google Scholar]
  5. Collins D. A., Chambers T. J. Effect of prostaglandins E1, E2, and F2 alpha on osteoclast formation in mouse bone marrow cultures. J Bone Miner Res. 1991 Feb;6(2):157–164. doi: 10.1002/jbmr.5650060209. [DOI] [PubMed] [Google Scholar]
  6. Collins D. A., Chambers T. J. Prostaglandin E2 promotes osteoclast formation in murine hematopoietic cultures through an action on hematopoietic cells. J Bone Miner Res. 1992 May;7(5):555–561. doi: 10.1002/jbmr.5650070512. [DOI] [PubMed] [Google Scholar]
  7. Dexter T. M., Allen T. D., Lajtha L. G. Conditions controlling the proliferation of haemopoietic stem cells in vitro. J Cell Physiol. 1977 Jun;91(3):335–344. doi: 10.1002/jcp.1040910303. [DOI] [PubMed] [Google Scholar]
  8. Flanagan A. M., Horton M. A., Dorey E. L., Collins D. A., Evely R. S., Moseley J. M., Firkin F. C., Chambers T. J., Helfrich M. H., Martin T. J. An assessment of the ability of human bone marrow cultures to generate osteoclasts. Int J Exp Pathol. 1992 Jun;73(3):387–401. [PMC free article] [PubMed] [Google Scholar]
  9. Flanagan A. M., Nui B., Tinkler S. M., Horton M. A., Williams D. M., Chambers T. J. The multinucleate cells in giant cell granulomas of the jaw are osteoclasts. Cancer. 1988 Sep 15;62(6):1139–1145. doi: 10.1002/1097-0142(19880915)62:6<1139::aid-cncr2820620617>3.0.co;2-8. [DOI] [PubMed] [Google Scholar]
  10. Horton M. A., Chambers T. J. Human osteoclast-specific antigens are expressed by osteoclasts in a wide range of non-human species. Br J Exp Pathol. 1986 Feb;67(1):95–104. [PMC free article] [PubMed] [Google Scholar]
  11. Horton M. A., Lewis D., McNulty K., Pringle J. A., Chambers T. J. Monoclonal antibodies to osteoclastomas (giant cell bone tumors): definition of osteoclast-specific cellular antigens. Cancer Res. 1985 Nov;45(11 Pt 2):5663–5669. [PubMed] [Google Scholar]
  12. Klein D. C., Raisz L. G. Prostaglandins: stimulation of bone resorption in tissue culture. Endocrinology. 1970 Jun;86(6):1436–1440. doi: 10.1210/endo-86-6-1436. [DOI] [PubMed] [Google Scholar]
  13. Kukita A., Chenu C., McManus L. M., Mundy G. R., Roodman G. D. Atypical multinucleated cells form in long-term marrow cultures from patients with Paget's disease. J Clin Invest. 1990 Apr;85(4):1280–1286. doi: 10.1172/JCI114565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kukita T., McManus L. M., Miller M., Civin C., Roodman G. D. Osteoclast-like cells formed in long-term human bone marrow cultures express a similar surface phenotype as authentic osteoclasts. Lab Invest. 1989 Apr;60(4):532–538. [PubMed] [Google Scholar]
  15. Kurihara N., Bertolini D., Suda T., Akiyama Y., Roodman G. D. IL-6 stimulates osteoclast-like multinucleated cell formation in long term human marrow cultures by inducing IL-1 release. J Immunol. 1990 Jun 1;144(11):4226–4230. [PubMed] [Google Scholar]
  16. Kurihara N., Chenu C., Miller M., Civin C., Roodman G. D. Identification of committed mononuclear precursors for osteoclast-like cells formed in long term human marrow cultures. Endocrinology. 1990 May;126(5):2733–2741. doi: 10.1210/endo-126-5-2733. [DOI] [PubMed] [Google Scholar]
  17. Kurland J. I., Bockman R. Prostaglandin E production by human blood monocytes and mouse peritoneal macrophages. J Exp Med. 1978 Mar 1;147(3):952–957. doi: 10.1084/jem.147.3.952. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lorenzo J. A., Sousa S. L., Van den Brink-Webb S. E., Korn J. H. Production of both interleukin-1 alpha and beta by newborn mouse calvarial cultures. J Bone Miner Res. 1990 Jan;5(1):77–83. doi: 10.1002/jbmr.5650050112. [DOI] [PubMed] [Google Scholar]
  19. MacDonald B. R., Takahashi N., McManus L. M., Holahan J., Mundy G. R., Roodman G. D. Formation of multinucleated cells that respond to osteotropic hormones in long term human bone marrow cultures. Endocrinology. 1987 Jun;120(6):2326–2333. doi: 10.1210/endo-120-6-2326. [DOI] [PubMed] [Google Scholar]
  20. Norrdin R. W., Jee W. S., High W. B. The role of prostaglandins in bone in vivo. Prostaglandins Leukot Essent Fatty Acids. 1990 Nov;41(3):139–149. doi: 10.1016/0952-3278(90)90081-u. [DOI] [PubMed] [Google Scholar]
  21. Shinar D. M., Rodan G. A. Biphasic effects of transforming growth factor-beta on the production of osteoclast-like cells in mouse bone marrow cultures: the role of prostaglandins in the generation of these cells. Endocrinology. 1990 Jun;126(6):3153–3158. doi: 10.1210/endo-126-6-3153. [DOI] [PubMed] [Google Scholar]
  22. Takahashi N., Akatsu T., Udagawa N., Sasaki T., Yamaguchi A., Moseley J. M., Martin T. J., Suda T. Osteoblastic cells are involved in osteoclast formation. Endocrinology. 1988 Nov;123(5):2600–2602. doi: 10.1210/endo-123-5-2600. [DOI] [PubMed] [Google Scholar]
  23. Tashjian A. H., Jr, Hohmann E. L., Antoniades H. N., Levine L. Platelet-derived growth factor stimulates bone resorption via a prostaglandin-mediated mechanism. Endocrinology. 1982 Jul;111(1):118–124. doi: 10.1210/endo-111-1-118. [DOI] [PubMed] [Google Scholar]
  24. Tashjian A. H., Jr, Levine L. Epidermal growth factor stimulates prostaglandin production and bone resorption in cultured mouse calvaria. Biochem Biophys Res Commun. 1978 Dec 14;85(3):966–975. doi: 10.1016/0006-291x(78)90638-1. [DOI] [PubMed] [Google Scholar]
  25. Tashjian A. H., Jr, Voelkel E. F., Lazzaro M., Goad D., Bosma T., Levine L. Tumor necrosis factor-alpha (cachectin) stimulates bone resorption in mouse calvaria via a prostaglandin-mediated mechanism. Endocrinology. 1987 May;120(5):2029–2036. doi: 10.1210/endo-120-5-2029. [DOI] [PubMed] [Google Scholar]

Articles from International Journal of Experimental Pathology are provided here courtesy of Wiley

RESOURCES