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International Journal of Experimental Pathology logoLink to International Journal of Experimental Pathology
. 1994 Aug;75(4):265–275.

Murine macrophage precursor cell lines are unable to differentiate into osteoclasts: a possible implication for osteoclast ontogeny.

R De Grooth 1, R H Mieremet 1, E W Kawilarang-De Haas 1, P J Nijweide 1
PMCID: PMC2002241  PMID: 7947229

Abstract

Six murine macrophage precursor cell lines, thought to be arrested around the CFU-GM stage of the myeloid differentiation and shown to be negative for acid phosphatase, F4/80 antigen expression and phagocytosis capacity, were tested for their ability to differentiate into osteoclasts. Their differentiation potential was compared with that of the haemopoietic stem cell line FDCP-mix C2GM. None of the macrophage precursor cell lines could be induced to differentiate into osteoclasts when the cells were cocultured with either periosteum-free metatarsal bones of fetal mice, or monolayers of osteoblast-like cells. In contrast, when the haemopoietic stem cell line FDCP-mix C2GM, murine fetal liver cells or murine spleen cells were used as a source of haemopoietic precursor cells, numerous osteoclasts were formed in both culture systems. During cell culture a small percentage of the macrophage precursor cells attached to the bottom of the culture well. These firmly attached cells acquired acid phosphatase activity, F4/80 antigen expression and phagocytosis capacity. Furthermore, when the cell lines were cultured for 2 or 4 days with 1% DMSO, up to 30% of the precursor cells differentiated into metamyelocytes. These results suggest that the macrophage precursor cell lines are able to acquire macrophage and granulocyte characteristics, but are unable to differentiate into osteoclasts. In contrast, the haemopoietic stem cell line FDCP-mix C2GM is able to differentiate into both macrophages and osteoclasts. We therefore suggest that the osteoclast lineage branches off at an early stage of the myeloid differentiation pathway.

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Selected References

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  1. Austyn J. M., Gordon S. F4/80, a monoclonal antibody directed specifically against the mouse macrophage. Eur J Immunol. 1981 Oct;11(10):805–815. doi: 10.1002/eji.1830111013. [DOI] [PubMed] [Google Scholar]
  2. Bazill G. W., Haynes M., Garland J., Dexter T. M. Characterization and partial purification of a haemopoietic cell growth factor in WEHI-3 cell conditioned medium. Biochem J. 1983 Mar 15;210(3):747–759. doi: 10.1042/bj2100747. [DOI] [PMC free article] [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., 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. Chambers T. J., McSheehy P. M., Thomson B. M., Fuller K. The effect of calcium-regulating hormones and prostaglandins on bone resorption by osteoclasts disaggregated from neonatal rabbit bones. Endocrinology. 1985 Jan;116(1):234–239. doi: 10.1210/endo-116-1-234. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Geurts van Kessel A. H., Tetteroo P. A., von dem Borne A. E., Hagemeijer A., Bootsma D. Expression of human myeloid-associated surface antigens in human-mouse myeloid cell hybrids. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3748–3752. doi: 10.1073/pnas.80.12.3748. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hagenaars C. E., Kawilarang-de Haas E. W., van der Kraan A. A., Spooncer E., Dexter T. M., Nijweide P. J. Interleukin-3-dependent hematopoietic stem cell lines capable of osteoclast formation in vitro. J Bone Miner Res. 1991 Sep;6(9):947–954. doi: 10.1002/jbmr.5650060908. [DOI] [PubMed] [Google Scholar]
  9. Hagenaars C. E., van der Kraan A. A., Kawilarang-de Haas E. W., Visser J. W., Nijweide P. J. Osteoclast formation from cloned pluripotent hemopoietic stem cells. Bone Miner. 1989 May;6(2):179–189. doi: 10.1016/0169-6009(89)90049-4. [DOI] [PubMed] [Google Scholar]
  10. Hattersley G., Chambers T. J. Effects of interleukin 3 and of granulocyte-macrophage and macrophage colony stimulating factors on osteoclast differentiation from mouse hemopoietic tissue. J Cell Physiol. 1990 Jan;142(1):201–209. doi: 10.1002/jcp.1041420125. [DOI] [PubMed] [Google Scholar]
  11. Hattersley G., Chambers T. J. Generation of osteoclasts from hemopoietic cells and a multipotential cell line in vitro. J Cell Physiol. 1989 Sep;140(3):478–482. doi: 10.1002/jcp.1041400311. [DOI] [PubMed] [Google Scholar]
  12. Hattersley G., Kerby J. A., Chambers T. J. Identification of osteoclast precursors in multilineage hemopoietic colonies. Endocrinology. 1991 Jan;128(1):259–262. doi: 10.1210/endo-128-1-259. [DOI] [PubMed] [Google Scholar]
  13. Ibbotson K. J., Roodman G. D., McManus L. M., Mundy G. R. Identification and characterization of osteoclast-like cells and their progenitors in cultures of feline marrow mononuclear cells. J Cell Biol. 1984 Aug;99(2):471–480. doi: 10.1083/jcb.99.2.471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. Lee M. Y., Eyre D. R., Osborne W. R. Isolation of a murine osteoclast colony-stimulating factor. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8500–8504. doi: 10.1073/pnas.88.19.8500. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lee M. Y., Lottsfeldt J. L., Fevold K. L. Identification and characterization of osteoclast progenitors by clonal analysis of hematopoietic cells. Blood. 1992 Oct 1;80(7):1710–1716. [PubMed] [Google Scholar]
  17. Leenen P. J., Slieker W. A., Melis M., Van Ewijk W. Murine macrophage precursor characterization. I. Production, phenotype and differentiation of macrophage precursor hybrids. Eur J Immunol. 1990 Jan;20(1):15–25. doi: 10.1002/eji.1830200104. [DOI] [PubMed] [Google Scholar]
  18. Loutit J. F., Nisbet N. W. The origin of osteoclasts. Immunobiology. 1982 Apr;161(3-4):193–203. doi: 10.1016/S0171-2985(82)80074-0. [DOI] [PubMed] [Google Scholar]
  19. Modderman W. E., Tuinenburg-Bol Raap A. C., Nijweide P. J. Tartrate-resistant acid phosphatase is not an exclusive marker for mouse osteoclasts in cell culture. Bone. 1991;12(2):81–87. doi: 10.1016/8756-3282(91)90004-3. [DOI] [PubMed] [Google Scholar]
  20. Modderman W. E., Vrijheid-Lammers T., Löwik C. W., Nijweide P. J. Removal of hematopoietic cells and macrophages from mouse bone marrow cultures: isolation of fibroblastlike stromal cells. Exp Hematol. 1994 Feb;22(2):194–201. [PubMed] [Google Scholar]
  21. Scheven B. A., Visser J. W., Nijweide P. J. In vitro osteoclast generation from different bone marrow fractions, including a highly enriched haematopoietic stem cell population. Nature. 1986 May 1;321(6065):79–81. doi: 10.1038/321079a0. [DOI] [PubMed] [Google Scholar]
  22. Spooncer E., Heyworth C. M., Dunn A., Dexter T. M. Self-renewal and differentiation of interleukin-3-dependent multipotent stem cells are modulated by stromal cells and serum factors. Differentiation. 1986;31(2):111–118. doi: 10.1111/j.1432-0436.1986.tb00391.x. [DOI] [PubMed] [Google Scholar]
  23. Suda T., Takahashi N., Martin T. J. Modulation of osteoclast differentiation. Endocr Rev. 1992 Feb;13(1):66–80. doi: 10.1210/edrv-13-1-66. [DOI] [PubMed] [Google Scholar]
  24. Takada Y., Kusuda M., Hiura K., Sato T., Mochizuki H., Nagao Y., Tomura M., Yahiro M., Hakeda Y., Kawashima H. A simple method to assess osteoclast-mediated bone resorption using unfractionated bone cells. Bone Miner. 1992 Jun;17(3):347–359. doi: 10.1016/0169-6009(92)90785-c. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Takahashi N., Udagawa N., Akatsu T., Tanaka H., Shionome M., Suda T. Role of colony-stimulating factors in osteoclast development. J Bone Miner Res. 1991 Sep;6(9):977–985. doi: 10.1002/jbmr.5650060912. [DOI] [PubMed] [Google Scholar]
  27. Udagawa N., Takahashi N., Akatsu T., Tanaka H., Sasaki T., Nishihara T., Koga T., Martin T. J., Suda T. Origin of osteoclasts: mature monocytes and macrophages are capable of differentiating into osteoclasts under a suitable microenvironment prepared by bone marrow-derived stromal cells. Proc Natl Acad Sci U S A. 1990 Sep;87(18):7260–7264. doi: 10.1073/pnas.87.18.7260. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. de Both N. J., Hagemeijer A., Rhijnsburger E. H., Vermey M., van't Hull E., Smit E. M. DMSO-induced terminal differentiation and trisomy 15 in myeloid cell line transformed by the Rauscher murine leukemia virus. Cell Differ. 1981 Jan;10(1):13–21. doi: 10.1016/0045-6039(81)90043-9. [DOI] [PubMed] [Google Scholar]

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