Abstract
Osteoclasts derive from a mononuclear haematopoietic precursor and are cells that resorb bone. They are rare cells, particularly in physiological states in adult primates, and osteoclasts that exist are difficult to harvest because they are situated on calcified bone surfaces within the medullary cavity. For these reasons the generation of osteoclasts from precursors using in vitro models has been of major interest to those involved in studying the biology of bone. The reproducible in vitro generation of osteoclasts, using a variety of murine organ and cell culture techniques, is well documented and reviewed and has advanced our knowledge of osteoclast biology [1–10]. The information accrued from these studies has recently led to the formation of cell lines in which a proportion of the cells formed are osteoclasts [8, 11]. Despite considerable effort, analogous studies using human haematopoietic cells have been less successful than those reported for murine systems and this chapter will concentrate on the difficulties involved in generating human osteoclasts in vitro.
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References
Takahashi, N., Akatsu, T., Udagawa, N. et al. (1988) Osteoblastic cells are involved in osteoclast formation. Endocrinology 123(5), 2600–2602.
Takahashi, N., Yamama, H., Yoshiki, S. et al. (1988) Osteoclast-like cell formation and its regulation by osteotropic hormones in mouse marrow cultures. Endocrinology 122), 1373–1382.
Hattersley, G. and Chambers, T.J. (1989) 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 125), 1606–1612.
Shinar, D.M., Sato, M. and Rodan, G.A. (1990) The effect of hemopoietic growth factors on the generation of osteoclast-like cells in mouse bone marrow cultures. Endocrinology 126(3), 1728–1735.
Akatsu, T., Tamura, T., Takahashi, N. et al. (1992) Preparation and characterization of mouse osteoclast-like multinucleate cell population. Journal of Bone and Mineral Research 7), 1297–1306.
Kerby, J.A., Hattersley, G., Collins, D.A. and Chambers, T.J. (1992) Derivation of osteoclasts from hematopoietic colony-forming cells in culture. Journal of Bone and Mineral Research 7(3), 353–362.
Tanaka, S., Takahashi, N., Udagawa, N. et al. (1993) Macrophage colony-stimulating factor is indispensable for both proliferation and differentiation of osteoclast progenitors. Journal of Clinical Investigation 91), 257–263.
Chambers, T.J., Owens, J.M., Hattersley, G. et al. (1993) Generation of osteoclast-inductive and osteoclastogenic cell lines from the H-2KbtsA58 transgenic mouse. Proceedings of the National Academy of Sciences USA 90), 5578–5582.
Quinn, J.M., McGee, J.O. and Athanasou, N.A. (1994) Cellular and hormonal factors influencing monocyte differentiation to osteoclast bone resorbing cells. Endocrinology 134), 2416–2223.
Wesolowski, G., Duong, L.T., Lakkakorpi, P.T. et al. (1995) Isolation and characterization of highly enriched, prefusion mouse osteoclastic cells. Experimental Cell Research 219), 679–686.
Ho Shin, J., Kukita, A., Ohki, K.P. et al. (1995) In vitro differentiation of the murine macrophage cell line BDM-1 into osteoclast-like cells. Endocrinology 136), 4285–4292.
Athanasou, N.A. and Quinn, J.(1990) Immunophenotypic differences between osteoclasts and macrophage polykaryons: immunohistochemical distinction and implications for osteoclast ontogeny and function. Journal of Clinical Pathology 43), 997–1003.
Warshawsky, J., Goltzman, D., Rouleau, M.F. and Bergeron, J.J.M. (1980) Direct in-vivo demonstration by autoradiography of specific binding sites for calcitonin in skeletal and renal tissues of the rat. Journal of Cell Biology 85), 682–694.
Nicholson, G.C., Moseley, J.M., Sexton, P.M. et al (1986) Abundant calcitonin receptors in isolated rat osteoclasts. Journal of Clinical Investigation 78), 355–360.
Flanagan, A.M., Horton, M.A., Dorey, E.L. et al (1992) An assessment of the ability of human bone marrow cultures to generate osteoclasts. International Journal of Experimental Pathology 73), 387–401.
Shinar, D.M. and Rodan, G.A. (1990) Biphasic effects of transforming growth factor β on the production of osteoclast-like cells in mouse bone marrow cultures: the role of prostaglandins in the generation of these cells. Endocrinology 126(6), 3153–3158.
Owens, J.M., Gallagher, A.C., Chambers, T.J. (1996) Bone cells required for osteoclastic resorption but not for osteoclastic differentiation. Biochemical and Biophysical Research Communications 222), 225–229.
Kaye, M. (1984) When is it an osteoclast? Journal of Clinical Pathology 37), 398–400.
Takahashi, N., Udagawa, N., Tanaka, S. et al. (1994) Postmitotic osteoclast precursors are mononuclear cells which express macrophage-associated phenotypes. Developmental Biology 163), 212–221.
Bianco, P., Costantini, M., Dearden, L.C. and Bonucci, E. (1987) Expression of tartrateresistant acid phosphatase in bone marrow macrophages. Basic Applied Histochemistry 31), 433–440.
Snipes, R.G., Lam, K.W., Dodd, R.C. et al (1986) Acid phosphatase in mononuclear phagocytes and the U937 cell line: monocyte-derived macrophages express tartrateresistant acid phosphatase. Blood 67), 729–734.
Yan, L.T., Li, C.Y. and Finkel, H.E. (1972) Leukemic reticuloendotheliosis. The role of tartrate-resistant acid phosphatase in diagnosis and splenectomy in treatment. Archives of Internal Medicine 130), 248–256.
Hattersley, G. and Chambers, T.J. (1989) Generation of osteoclastic function in mouse bone marrow cultures: multinuclearity and tartrate-resistant acid phosphatase are unreliable markers for osteoclastic differentiation. Endocrinology 124), 1689–1696.
Horton, M.A., Rimmer, E.F., Lewis, D. et al. (1984) Cell surface phenotype of the human osteoclast: phenotypic relationship to other bone marrow derived cell types. Journal of Pathology 144), 281–294.
Horton, M.A., Lewis, D., McNulty, K. et al. (1985) Monoclonal antibodies to osteoclastomas (giant cell bone tumours): definition of osteoclast-specific cellular antigens. Cancer Research 45), 5663–5669.
Flanagan, A.M., Tinkler, S.M.B., Horton, M.A. et al. (1988) The multinucleate cells in giant cell granulomas of the jaw are osteoclasts. Cancer 62), 1139–1145.
Flanagan, A.M. and Chambers, T.J. (1989) Osteoclasts are present in the giant cell variant of malignant fibrous histiocytoma. Journal of Pathology 159), 53–57.
Horton, M.A., Lewis, D., McNulty, K. et al. (1985) Human fetal osteoclasts fail to express macrophage antigens. British Journal of Experimental Pathology 66), 103–108.
Davies, J., Warwick, J., Tutty, N. et al. (1989) The osteoclast functional antigen, implicated in the regulation of bone resorption, is biochemically related to the vitronectin receptor. Journal of Cell Biology 109), 1817–1826.
MacDonald, B.R., Mundy, G.R., Clark, S. et al. (1986) Effects of human recombinant CSF-GM and highly purified CSF-1 on the formation of multinucleated cells with osteoclast characteristics in long-term bone marrow cultures. Journal of Bone and Mineral Research 1), 227–233.
Chenu, C, Pfeilschifter, J., Mundy, G.R. and Roodman, G.D. (1988) Transforming growth factor β inhibits formation of osteoclast-like cells in long-term human marrow cultures. Proceedings of the National Academy of Sciences USA 85), 5683–5687.
Hughes, D.E., MacDonald, B.R., Russell, R.G.G. and Gowen, M. (1989) Inhibition of osteoclast-like cell formation by bisphosphonates in long-term cultures of human bone marrow. Journal of Clinical Investigation 83), 1930–1935.
Kukita, A., Bouewald, L., Rosen, D. et al. (1990) Osteoinductive factor inhibits formation of human osteoclast-like cells. Proceedings of the National Academy of Sciences USA 87), 3023–3026.
Kukita, T. and Roodman, G.D. (1989) Development of a monoclonal antibody to osteoclasts formed in vitro which recognizes mononuclear osteoclast precursors in the marrow. Endocrinology 125), 630–637.
Kukita, T., McManus, L.M., Civin, C. and Roodman, G.D. (1989) Osteoclast-like cells formed in long-term human bone marrow cultures express a similar surface phenotype as authentic osteoclasts. Laboratory Investigation 60), 532–538.
Takahashi, N., Kukita, T., MacDonald, B.R. et al. (1989) Osteoclast-like cells form in long-term human bone marrow but not in peripheral blood. Journal of Clinical Investigation 84), 543–550.
Chenu, C., Kurihara, N., Mundy, G.R. and Roodman, G.D. (1990) Prostaglandin E2 inhibits formation of osteoclast-like cells in long-term human marrow cultures but is not a mediator of the inhibitory effects of transforming growth factor β. Journal of Bone and Mineral Research 5), 677–687.
Kurihara, N., Gluck, S. and Roodman, G.D. (1990) Sequential expression of phenotype markers for osteoclasts during differentiation of precursors for multinucleated cells formed in long term human marrow cultures. Endocrinology 127(6), 3215–3221.
Kurihara, N., Bertolini, D., Suda, T. et al. (1990) IL-6 stimulated osteoclast-like multinucleated cell formation in long-term human cultures by inducing IL-1 release. Journal of Immunology 144), 4226–4230.
Kurihara, N., Chenu, C., Miller, M. et al. (1990) Identification of committed mononuclear precursors for osteoclast-like cells formed in long term human marrow cultures. Endocrinology 126(5), 2733–2741.
Thavarajah, M., Evans, D.B., Binderup, L. and Kanis, J.A. (1990) 1,25(OH)2D3 and calcipotriol (MC903) have similar effects on the induction of osteoclast-like cell formation in human bone marrow cultures. Endocrinology 125), 630–637.
Roodman, G.D. (1995) Application of bone marrow cultures to the study of osteoclast formation and osteoclast precursors in man. Calcified Tissue International 56(Suppl. 1), S22–S23.
Pacifici, R. (1995) Cytokines and osteoclast activity. Calcified Tissue International 56), S27–S28.
Sarma, U. and Flanagan, A.M. (1996) Macrophage-colony stimulating factor (M-CSF) induces substantial osteoclast formation in human bone-marrow cultures. Blood 88), 2531–2540.
Wiktor-Jedrzejczak, W., Bartocci, A., Ferrante, A.W. Jr et al. (1990) Total absence of colony-stimulating factor 1 in the macrophage-deficient osteopetrotic (op/op) mouse. Proceedings of the National Academy of Sciences USA 87), 4828–4832.
Felix, R., Cecchini, M.G., Hofstetter, W. et al. (1990) Impairment of macrophage colony-stimulating factor production and lack of resident bone marrow macrophages in the osteopetrotic op/op mouse. Journal of Bone and Mineral Research 5), 781–789.
Felix, R., Cecchini, M.G. and Heisch, H. (1990) Macrophage colony stimulating factor restores in vivo bone resorption in the op/op osteopetrotic mouse. Endocrinology 127(6), 2592–2594.
Kodama, H., Yamasaki, A., Abe, M. et al. (1993) Transient recruitment of osteoclasts and expression of their function in osteopetrotic (op/op) mice by a single injection of macrophage colony-stimulating factor. Journal of Bone and Mineral Research 8), 45–50.
Yoshida, H., Hayashi, S.-I., Kunisada, T. et al. (1990) The murine mutation osteopetrosis is in the coding region of the macrophage colony stimulating factor gene. Nature 345), 442–444.
Mbalaviele, G., Orcel, P., Morieux, C. et al. (1995) Osteoclast formation from human cord blood mononuclear cells co-cultured with mice embryonic metatarsals in the presence of M-CSF. Bone 16), 171–177.
Takahashi, N., Udagawa, N., Akatsu, T. et al. (1991) Role of colony-stimulating factors in osteoclast development. Journal of Bone and Mineral Research 6), 977–985.
Hattersley, G. and Chambers, T.J. (1990) Effects of interleukin 3 and of granulocyte-macrophage and macrophage colony stimulating factors on osteoclast differentiation from mouse hemopoietic tissue. Journal of Cellular Physiology 142), 201–209.
Jaworski, Z.F.G., Duck, B. and Sekaly, G. (1981) Kinetics of osteoclasts and their nuclei in evolving secondary Haversian systems. Journal of Anatomy 133), 397–405.
Loutit, J.F. and Townsend, K.M.S. (1982) Longevity of osteoclasts in radiation chimeras of osteopetrotic beige and normal mice. British Journal of Experimental Pathology 63), 221–223.
Marks, S.C. Jr and Schneider, G.B. (1982) Transformation of osteoclast phenotype in rats cured of congenital osteopetrosis. Journal of Morphology 174), 141–147.
Fuller, K., Owens, J.M., Jagger, C. J. et al. (1993) Macrophage colony-stimulating factor stimulates survival and chemotactic behavior in isolated osteoclasts. Journal of Experimental Medicine 178), 1733–1744.
Fuller, K. and Chambers, T.J. (1987) Generation of osteoclasts in cultures of rabbit bone marrow and spleen cells. Journal of Cellular Physiology 132), 441–452.
Flanagan, A.M., Stow, M.D. and Williams, R. (1995) The effect of interleukin-6 and soluble interleukin-6 receptor protein on the bone resorptive activity of human osteoclasts generated in vitro. Journal of Pathology 176), 289–297.
Flanagan, A.M., Stow, M.D., Kendall, N. and Brace, W. (1995) The role of dihydroxyvitamin D3 and prostaglandin E2 in the regulation of human osteoclastic bone resorption. International Journal of Experimental Pathology 76), 37–42.
Fujikawa, Y., Quinn, J.M.W., Sabokbar, A. et al (1996) The human osteoclast precursor circulates in the monocyte fraction. Endocrinology 137), 4058–4060.
Quinn, J.M.W., McGee, J.O. and Athanasou, N.A. (1994) Cellular and hormonal factors influencing monocyte differentiation to osteoclastic bone-resorbing cells. Endocrinology 134), 2416–2423.
Hunter, W.M. and Greenwood, F.C. (1962) Preparation of iodine 131 labelled human growth hormone of high specific activity. Nature 194), 495.
Saema, U., Edwards, M., Motoyoshi, K. and Flanagan, A.M. (1997) Inhibition of bone resorption by 17β-estradiol in human bone-marrow cultures. Journal of Cellular Physiology. In press.
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Flanagan, A.M., Sarma, U. (1998). In vitro models for osteoclast recruitment . In: Arnett, T.R., Henderson, B. (eds) Methods in Bone Biology. Springer, Boston, MA. https://doi.org/10.1007/978-0-585-38227-2_2
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DOI: https://doi.org/10.1007/978-0-585-38227-2_2
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