Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1990 Sep;87(18):7260–7264. doi: 10.1073/pnas.87.18.7260

Origin of osteoclasts: mature monocytes and macrophages are capable of differentiating into osteoclasts under a suitable microenvironment prepared by bone marrow-derived stromal cells.

N Udagawa 1, N Takahashi 1, T Akatsu 1, H Tanaka 1, T Sasaki 1, T Nishihara 1, T Koga 1, T J Martin 1, T Suda 1
PMCID: PMC54723  PMID: 2169622

Abstract

We previously reported that osteoclast-like cells were formed in cocultures of a mouse marrow-derived stromal cell line (ST2) with mouse spleen cells in the presence of 1 alpha, 25-dihydroxyvitamin D3 and dexamethasone. In this study, we developed a new coculture system to determine the origin of osteoclasts. When relatively small numbers of mononuclear cells (10(3)-10(5) cells per well) obtained from mouse bone marrow, spleen, thymus, or peripheral blood were cultured for 12 days on the ST2 cell layers, they formed colonies with a linear relationship between the number of colonies formed and the number of hemopoietic cells inoculated. Tartrate-resistant acid phosphatase (TRAPase)-positive mononuclear and multinucleated cells appeared in the colonies (TRAPase-positive colonies) in response to 1 alpha, 25-dihydroxyvitamin D3 and dexamethasone. When hemopoietic cells suspended in a collagen-gel solution were cultured on the ST2 cell layers to prevent their movement, TRAPase-positive colonies were similarly formed, indicating that each colony originated from a single cell. All of the colonies consisted of nonspecific esterase-positive cells. The monocyte-depleted population prepared from peripheral blood failed to form colonies, whereas the monocyte-enriched population produced a large number of TRAPase-positive colonies. In addition, alveolar macrophages formed TRAPase-positive colonies most efficiently on the ST2 cell layers in the presence of the two hormones. Salmon 125I-labeled calcitonin specifically bound to the TRAPase-positive cells. Resorption lacunae were formed on dentine slices on which cocultures were performed. When direct contact between the peripheral blood cells and the ST2 cells was inhibited by a collagen-gel sheet, no TRAPase-positive cells were formed. These results indicate that osteoclasts are also derived from the mature monocytes and macrophages when a suitable microenvironment is provided by bone marrow-derived stromal cells.

Full text

PDF
7260

Images in this article

7261Image
on p.7261
7262Image
on p.7262
7263Image
on p.7263
7264Image
on p.7264

Selected References

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

  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. Akagawa K. S., Kamoshita K., Tokunaga T. Effects of granulocyte-macrophage colony-stimulating factor and colony-stimulating factor-1 on the proliferation and differentiation of murine alveolar macrophages. J Immunol. 1988 Nov 15;141(10):3383–3390. [PubMed] [Google Scholar]
  3. Boyde A., Ali N. N., Jones S. J. Resorption of dentine by isolated osteoclasts in vitro. Br Dent J. 1984 Mar 24;156(6):216–220. doi: 10.1038/sj.bdj.4805313. [DOI] [PubMed] [Google Scholar]
  4. Burger E. H., van der Meer J. W., Nijweide P. J. Osteoclast formation from mononuclear phagocytes: role of bone-forming cells. J Cell Biol. 1984 Dec;99(6):1901–1906. doi: 10.1083/jcb.99.6.1901. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chambers T. J., Horton M. A. Failure of cells of the mononuclear phagocyte series to resorb bone. Calcif Tissue Int. 1984 Sep;36(5):556–558. doi: 10.1007/BF02405365. [DOI] [PubMed] [Google Scholar]
  6. Chambers T. J., Magnus C. J. Calcitonin alters behaviour of isolated osteoclasts. J Pathol. 1982 Jan;136(1):27–39. doi: 10.1002/path.1711360104. [DOI] [PubMed] [Google Scholar]
  7. Felix R., Cecchini M. G., Hofstetter W., Elford P. R., Stutzer A., Fleisch H. Impairment of macrophage colony-stimulating factor production and lack of resident bone marrow macrophages in the osteopetrotic op/op mouse. J Bone Miner Res. 1990 Jul;5(7):781–789. doi: 10.1002/jbmr.5650050716. [DOI] [PubMed] [Google Scholar]
  8. Göthlin G., Ericsson J. L. On the histogenesis of the cells in fracture callus. Electron microscopic autoradiographic observations in parabiotic rats and studies on labeled monocytes. Virchows Arch B Cell Pathol. 1973 Mar 30;12(4):318–329. [PubMed] [Google Scholar]
  9. Hattersley G., Chambers T. J. Calcitonin receptors as markers for osteoclastic differentiation: correlation between generation of bone-resorptive cells and cells that express calcitonin receptors in mouse bone marrow cultures. Endocrinology. 1989 Sep;125(3):1606–1612. doi: 10.1210/endo-125-3-1606. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Horton M. A., Rimmer E. F., Lewis D., Pringle J. A., Fuller K., Chambers T. J. Cell surface characterization of the human osteoclast: phenotypic relationship to other bone marrow-derived cell types. J Pathol. 1984 Dec;144(4):281–294. doi: 10.1002/path.1711440410. [DOI] [PubMed] [Google Scholar]
  12. JEE W. S., NOLAN P. D. ORIGIN OF OSTEOCLASTS FROM THE FUSION OF PHAGOCYTES. Nature. 1963 Oct 19;200:225–226. doi: 10.1038/200225a0. [DOI] [PubMed] [Google Scholar]
  13. Kahn A. J., Simmons D. J. Investigation of cell lineage in bone using a chimaera of chick and quial embryonic tissue. Nature. 1975 Nov 27;258(5533):325–327. doi: 10.1038/258325a0. [DOI] [PubMed] [Google Scholar]
  14. Ly I. A., Mishell R. I. Separation of mouse spleen cells by passage through columns of sephadex G-10. J Immunol Methods. 1974 Aug;5(3):239–247. doi: 10.1016/0022-1759(74)90108-2. [DOI] [PubMed] [Google Scholar]
  15. Marks S. C., Jr Osteopetrosis in the toothless (t1) rat: presence of osteoclasts but failure to respond to parathyroid extract or to be cured by infusion of spleen or bone marrow cells from normal littermates. Am J Anat. 1977 Jun;149(2):289–297. doi: 10.1002/aja.1001490212. [DOI] [PubMed] [Google Scholar]
  16. Nicholson G. C., Moseley J. M., Sexton P. M., Mendelsohn F. A., Martin T. J. Abundant calcitonin receptors in isolated rat osteoclasts. Biochemical and autoradiographic characterization. J Clin Invest. 1986 Aug;78(2):355–360. doi: 10.1172/JCI112584. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Nishikawa S., Ogawa M., Nishikawa S., Kunisada T., Kodama H. B lymphopoiesis on stromal cell clone: stromal cell clones acting on different stages of B cell differentiation. Eur J Immunol. 1988 Nov;18(11):1767–1771. doi: 10.1002/eji.1830181117. [DOI] [PubMed] [Google Scholar]
  18. Ogawa M., Nishikawa S., Ikuta K., Yamamura F., Naito M., Takahashi K., Nishikawa S. B cell ontogeny in murine embryo studied by a culture system with the monolayer of a stromal cell clone, ST2: B cell progenitor develops first in the embryonal body rather than in the yolk sac. EMBO J. 1988 May;7(5):1337–1343. doi: 10.1002/j.1460-2075.1988.tb02949.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Schneider G. B., Relfson M. A bone marrow fraction enriched for granulocyte-macrophage progenitors gives rise to osteoclasts in vitro. Bone. 1988;9(5):303–308. doi: 10.1016/8756-3282(88)90014-2. [DOI] [PubMed] [Google Scholar]
  20. Shinar D. M., Sato M., Rodan G. A. The effect of hemopoietic growth factors on the generation of osteoclast-like cells in mouse bone marrow cultures. Endocrinology. 1990 Mar;126(3):1728–1735. doi: 10.1210/endo-126-3-1728. [DOI] [PubMed] [Google Scholar]
  21. Takahashi N., Akatsu T., Sasaki T., Nicholson G. C., Moseley J. M., Martin T. J., Suda T. Induction of calcitonin receptors by 1 alpha, 25-dihydroxyvitamin D3 in osteoclast-like multinucleated cells formed from mouse bone marrow cells. Endocrinology. 1988 Sep;123(3):1504–1510. doi: 10.1210/endo-123-3-1504. [DOI] [PubMed] [Google Scholar]
  22. Takahashi N., Yamana H., Yoshiki S., Roodman G. D., Mundy G. R., Jones S. J., Boyde A., Suda T. Osteoclast-like cell formation and its regulation by osteotropic hormones in mouse bone marrow cultures. Endocrinology. 1988 Apr;122(4):1373–1382. doi: 10.1210/endo-122-4-1373. [DOI] [PubMed] [Google Scholar]
  23. Udagawa N., Takahashi N., Akatsu T., Sasaki T., Yamaguchi A., Kodama H., Martin T. J., Suda T. The bone marrow-derived stromal cell lines MC3T3-G2/PA6 and ST2 support osteoclast-like cell differentiation in cocultures with mouse spleen cells. Endocrinology. 1989 Oct;125(4):1805–1813. doi: 10.1210/endo-125-4-1805. [DOI] [PubMed] [Google Scholar]
  24. Walker D. G. Congenital osteopetrosis in mice cured by parabiotic union with normal siblings. Endocrinology. 1972 Oct;91(4):916–920. doi: 10.1210/endo-91-4-916. [DOI] [PubMed] [Google Scholar]
  25. Walker D. G. Control of bone resorption by hematopoietic tissue. The induction and reversal of congenital osteopetrosis in mice through use of bone marrow and splenic transplants. J Exp Med. 1975 Sep 1;142(3):651–663. doi: 10.1084/jem.142.3.651. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Walker D. G. Osteopetrosis cured by temporary parabiosis. Science. 1973 May 25;180(4088):875–875. doi: 10.1126/science.180.4088.875. [DOI] [PubMed] [Google Scholar]
  27. Yoshida H., Hayashi S., Kunisada T., Ogawa M., Nishikawa S., Okamura H., Sudo T., Shultz L. D., Nishikawa S. The murine mutation osteopetrosis is in the coding region of the macrophage colony stimulating factor gene. Nature. 1990 May 31;345(6274):442–444. doi: 10.1038/345442a0. [DOI] [PubMed] [Google Scholar]
  28. Zambonin Zallone A., Teti A., Primavera M. V. Monocytes from circulating blood fuse in vitro with purified osteoclasts in primary culture. J Cell Sci. 1984 Mar;66:335–342. doi: 10.1242/jcs.66.1.335. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES