Summary
Cells obtained from surgical bone specimens of eight patients with Paget’s disease of bone were maintained in culture for up to 8 months and seven passages. The doubling time during the period of maximal cell growth ranged from 4 to 12 days. Evidence consistent with the hypothesis that many of the cells were bone cells included the following: (a) histochemical techniques demonstrated staining of some cells for alkaline phosphatase or acid phosphatase and succinic dehydrogenase; (b) parathyroid extract stimulated increased uptake of3H-thymidine and3H-uridine; (c) parathyroid extract suppressed and salmon calcitonin stimulated uptake of3H-proline; and (d) crystalline calcium deposits were found within cells and extracellularly.
Ultrastructural analysis revealed that three of the eight cultures contained cells whose nuclei had inclusions which were almost identical to those found in the osteoclast nuclei of all patients with Paget’s disease. The maintenance of cells derived from pagetic bone in long-term culture should aid in testing the hypothesis that Paget’s disease represents a slow virus infection of bone.
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Rebel, A., Malkani, K., Basle, M.: Anomalies nucleaires des osteoclasts de la maladie osseuse de Paget, Nouv. Presse Med.3:1299–1301, 1974
Baldet, P.: La Maladie Osseuse de Paget. Premier Collique de Pathologie Locomotrice, p. 73. Paris Galliena, Montpellier, 1975
Mills, B.G., Singer, F.R.: Nuclear inclusions in Paget’s disease of bone, Science194:201–202, 1976
Schultz A., Delling, G., Ringe, J.-D., Ziegler, R.: Untersuchungen zur ultrastruktur der osteoclasten und ihrer cytopathogenese, Virchows Arch. [Pathol. Anat.]376:309–328, 1977
Oyanagi, S., ter Meulen, V., Katz, M., Koprowski, H.: Comparison of subacute sclerosing panencephalitis and measles viruses: an electron microscope study, J. Virol.7:176–187, 1971
Horta-Barbosa, L., Fuccillo, D.A., Sever, J.L., Zeman, W.: Subacute sclerosing panencephalitis: isolation of measles virus from a brain biopsy, Nature221:974–975, 1969
Merchant, D.J., Kahn, R.H., Murphy, W.H.,Jr.: Handbook of Cell and Organ Culture, pp. 207–209. Burgess Publ. Co., Minneapolis, 1964
Mills, B.G., Holst, P., Haroutinian, A.M., Bavetta, L.A.: Bone cell response to serum calcium altering drugs, Clin. Orthop.78:56–82, 1971
Humason, G.L.: Animal Tissue Techniques, pp. 261–263. W.H. Freeman & Co., San Francisco, 1967
Smith, D.M., Johnston, C.C.,Jr., Severson, A.R.: Studies of the metabolism of separated bone cells, Calcif. Tissue Res11:56–69, 1973
Walker, D.G.: Enzymatic and electron microscopic analysis of isolated osteoclasts, Calcif. Tissue Res.9:296–309, 1972
Fullmer, H.M., Link, C.C.,Jr., Baer, M.J.: A stain for bone illustrating apposition and absorption in two colors, Stain Technol.39:71–73, 1964
Sigma Technical Bulletin No. 85: The histochemical demonstration of phosphatase in blood smears or tissue sections, p. 1. Sigma Chemical Co., St. Louis, 1963
Sigma Technical Bulletin No. 840: The histochemical demonstration of nitroblue tetrazolium (NBT) reduction in neutrophils, pp. 1–15. Sigma Chemical Co., St. Louis, 1978
Humason, G.L.: Animal Tissue Techniques, pp. 416–417. W.H. Freeman & Co., San Francisco, 1967
Dayer, J.-M., Krane, S.M., Russell, R.G.G., Robinson, D.R.: Production of collagenase and prostaglandins by isolated adherent rheumatoid synovial cells, Proc. Natl. Acad. Sci. U.S.A.73:945–949, 1976
Martin, G.R., Mecca, C.E., Schiffmann, E., Goldhaber, P.: Alterations in bone metabolism induced by parathyroid extract. In P.J. Gaillard, R.V. Talmage, A.M. Budy (eds.): The Parathyroid Glands, pp. 261–272. University of Chicago Press, Chicago, 1965
Peck, W.A., Messinger, K., Kimmich, G., Carpenter, J.: Stimulation of uridine incorporation in isolated bone cells by parathyroid hormone and cyclic AMP, J. Endocrinol.95:289–298, 1974
Bingham, P.J., Brazell, I.A., Owen, M.A.: The effect of parathyroid extract on cellular activity and plasma calcium levelsin vivo, J. Endocrinol45:387–400, 1969
Rechler, M.M., Podskalny, J.M., Goldfine, I.D., Wells, C.A.: DNA synthesis in human fibroblasts: stimulation by insulin and by non-suppressible insulin-like activity (NSILA-S), J. Clin. Endocrinol. Metab.39:512–521, 1974
Tamm, I., Hand, R., Caliguiri, L.A.: Action of dichlorobenzimidazole riboside on RNA synthesis in L-929 and HeLa cells, J. Cell Biol.69:229–240, 1976
Raisz, L.G., Dietrich, J.W., Canalis, E.M.: Factors influencing bone formation in organ culture, Isr. J. Med. Sci.12:108–114, 1976
Miller, S.S., Wolf, A.M., Arnaud, C.D.: Bone cells in culture: Morphologic transformation by hormones, Science192:1340–1342, 1976
Yagiela, J.A., Woodbury, D.M.: Enzymatic isolation of osteoblasts from fetal calvaria, Anat. Rec.188:287–305, 1977
Binderman, I., Duksin, D., Harell, A., Katzir, E., Sachs, L.: Formation of bone tissue in culture from isolated bone cells, J. Cell Biol.61:427–439, 1974
Luben, R.A., Wong, G.L., Cohn, D.V.: Biochemical characterization with parathormone and calcitonin of isolated bone cells: provisional identification of osteoclasts and osteoblasts, Endocrinology99:526–534, 1976
Osdoby, P., Caplan, A.I.: The possible differentiation of osteogenic elements in vitro from chick limb mesenchymal cells, Dev. Biol.52:283–299, 1976
Rose, G.G., Shindler, T.O.: The mineralization of emigrating bone cells in tissue culture, Tex. Rep. Biol. Med.22:174–188, 1964
Bard, D.R., Dickens, M.J., Edwards, J., Smith, A.V.: Ultrastructure, in vitro cultivation and metabolism of cells isolated from arthritic human bone, J. Bone Joint Surg.56B:352–360, 1974
Rasmussen, H., Bordier, P.: The Physiological and Cellular Basis of Metabolic Bone Disease, p. 154. Williams & Wilkins Co., Baltimore, 1974
Mills, B.G., Haroutinian, A.M., Holst, P., Bordier, P.J., Tun-Chot, S.: Ultrastructural and cellular changes at the costochondral junction following in vivo treatment with calcitonin or calcium chloride in the rabbit. In Selwyn, Taylor (ed.): Endocrinology 1971, pp. 77–88. William Heinemann Medical Books Ltd., London, 1972
Kather, H., Simon, B.: Adenylate cyclase of human fat cell ghosts, J. Clin. Invest.59:730–733, 1977
Goldring, S.R., Dayer, J.-M., Russell, R.G.G., Mankin, H.J., Krane, S.M.: Response to hormones of cells cultured from human giant cell tumor of bone, J. Clin. Endocrinol. Metab.46:425–433, 1978
Marx, S.J., Aurbach, G.D., Gavin, J.R.,3rd, Buell, D.W.: Calcitonin receptors on cultured human lymphocytes, J. Biol. Chem.249:6812–6816, 1974
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Mills, B.G., Singer, F.R., Weiner, L.P. et al. Long-term culture of cells from bone affected by Paget’s disease. Calcif Tissue Int 29, 79–87 (1979). https://doi.org/10.1007/BF02408061
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DOI: https://doi.org/10.1007/BF02408061