Advertisement

The Skeleton pp 195-213 | Cite as

Osteoclast Differentiation

  • Sakamuri V. Reddy
  • G. David Roodman
Chapter

Abstract

The osteoclast is the primary bone-resorbing cell and the majority of evidence favors that it is derived from the monocyte—macrophage lineage, although recently there have been reports that early B lymphocytes, B220+ cells can also form osteoclasts (1). The earliest identifiable osteoclast precursor is the granulocyte-macrophage colony-forming unit (CFU-GM), the granulocyte-macrophage progenitor cells that proliferate and differentiate into committed precursors for the osteoclast (2). These committed precursors are postmitotic and fuse to form multinucleated osteoclasts. These multinucleated cells (MNCs) are then activated to form bone-resorbing osteoclasts. After a prescribed period of time, the cells undergo apoptosis. The life cycle of the osteoclast is depicted in Fig. 1. The molecular and cellular events involved in osteoclast differentiation and the large array of factors regulating osteoclast formation and activity are just beginning to be defined. In this review, the factors that are known to be critical to osteoclast differentiation and the genes involved in this process will be discussed.

Keywords

Bone Resorption Stromal Cell Osteoblastic Cell Osteoclast Differentiation Osteoclast Formation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Sato, T., Shibata, T., Ikeda, K., and Watanabe, K. (2001) Generation of bone resorbing osteoclasts from B220+ cells: its role in accelerated osteoclastogenesis due to estrogen deficiency. J. Bone Miner Res. 16, 2215–2221.PubMedCrossRefGoogle Scholar
  2. 2.
    Menaa, C., Kurihara, N., and Roodman, G. D. (2000) CFU-GM-derived cells form osteoclasts at a very high efficiency. Biochem. Biophys. Res. Commun. 267, 943–946.PubMedCrossRefGoogle Scholar
  3. 3.
    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.PubMedCrossRefGoogle Scholar
  4. 4.
    Horton, M. A., Lewis, D., McNulty, K., Pringle, J. A. S., and Chambers, T. J. (1985) Monoclonal antibodies to osteoclastomas (giant cell bone tumors): definition of osteoclast-specific cellular antigens. Cancer Res. 45, 5663–5669.PubMedGoogle Scholar
  5. 5.
    Suda, T., Udagawa, N., Nakamura, I., Miyaura, C., and Takahashi, N. (1995) Modulation of osteoclast differentiation by local factors. Bone 17, 87S–91S.PubMedCrossRefGoogle Scholar
  6. 6.
    Kania, J. R., Kehat-Stadler, T., and Kupfer, S. R. (1997) CD44 antibodies inhibit osteoclast formation. J. Bone Miner. Res. 12, 1155–1164.PubMedCrossRefGoogle Scholar
  7. 7.
    Takahashi, S., Goldring, S., Katz, M., Hilsenbeck, S., Williams, R., and Roodman, G. D. (1995) Downregulation of calcitonin receptor mRNA expression by calcitonin during human osteoclast-like cell differentiation. J. Clin. Invest. 95, 167–171.PubMedCrossRefGoogle Scholar
  8. 8.
    Hayman, A. R., Jones, S. J., Boyde, A., Foster, D., Colledge, W. H., Carlton, M. B., et al. (1996) Mice lacking tartrate-resistant acid phosphatase (Acp 5) have disrupted endochondral ossification and mild osteopetrosis. Development 122, 3151–3162.PubMedGoogle Scholar
  9. 9.
    Halleen, J. M., Raisanen, S., Salo, J. J., Reddy, S. V., Roodman, G. D., Hentunen, T. A., et al. (1999) Intracellular fragmentation of bone resorption products by reactive oxygen species generated by osteoclastic tartrate resistant acid phosphatase. J. Biol. Chem. 274, 22907–22910.PubMedCrossRefGoogle Scholar
  10. 10.
    Sato, T., Abe, E., Jin, C. H., Hong, M. H., Katagiri, T., Kinoshita, T., et al. (1993) The biological roles of the third component of complement in osteoclast formation. Endocrinology 133, 397–404.PubMedCrossRefGoogle Scholar
  11. 11.
    Oursler, M. J. (1994) Osteoclast synthesis, secretion and activation of latent transforming growth factor beta. J. Bone Miner. Res. 9, 443–452PubMedCrossRefGoogle Scholar
  12. 12.
    Takahashi, S., Reddy, S. V., Chirgwin, J. M., Devlin, R. D., Haipek, C., Anderson, J., et al. (1994) Cloning and characterization of Annexin II as an autocrine/paracrine factor that increases osteoclast formation and bone resorption. J. Biol. Chem. 269, 28696–28701.PubMedGoogle Scholar
  13. 13.
    Menaa, C., Devlin, R. D., Reddy, S. V., Gazitt, Y., Choi, S., and Roodman, G. D. (1999) Annexin II increases osteoclast formation by stimulating the proliferation of osteoclast precursors in human marrow cultures. J. Clin. Invest. 103, 1605–1613.PubMedCrossRefGoogle Scholar
  14. 14.
    Kurihara, N., Menaa, C., Haile, D. J., and Reddy, S. V. (2001) Osteoclast stimulatory factor (OSF) interacts with the spinal muscular atrophy (SMA) gene product to stimulate osteoclast formation. J. Biol. Chem. 276, 41035–41039.PubMedCrossRefGoogle Scholar
  15. 15.
    Choi, S., Devlin, R. D., Menaa, C., Chung, H., and Roodman, G. D., and Reddy S. V. (1988) Cloning and identification of human Sca as a novel inhibitor of osteoclast formation and bone resorption. J. Clin. Invest. 102, 1360–1368.CrossRefGoogle Scholar
  16. 16.
    Choi, S., Reddy, S. V., Devlin, R. D., Menaa, C., Chung, H., Boyce, B. F., et al. 1999) Identification of human Asparaginyl endopeptidase (Legumain) as an inhibitor of osteoclast formation and bone resorption. J. Biol. Chem. 274, 27747–27753.PubMedCrossRefGoogle Scholar
  17. 17.
    Koide, M., Kurihara, N., Maeda, H., and Reddy, S. V. (2002) Identification of the functional domain of osteoclast inhibitory peptide- 1 /hSca. J. Bone Miner. Res. 17, 111–118.PubMedCrossRefGoogle Scholar
  18. 18.
    Koide, M., Maeda, H., Roccisana, J. L., and Reddy, S. V. (2003) Cytokine regulation and the signaling mechanism of osteoclast inhibitory peptide-1 (0IP-1/hSca) to inhibit osteoclast formation. J. Bone Miner. Res. 18, 458–465.PubMedCrossRefGoogle Scholar
  19. 19.
    Choi, S. J., Han, J. H., and Roodman, G. D. (2001) ADAM8: a novel osteoclast stimulating factor. J. Bone Miner. Res. 16, 814–822.PubMedCrossRefGoogle Scholar
  20. 20.
    Takahashi, N., Akatsu, T., Udagawa, N., Sasaki, T., Yamaguchi, A., Moseley, J. M., et al. (1988) Osteoblastic cells are involved in osteoclast formation. Endocrinology 123, 2600–2602.PubMedCrossRefGoogle Scholar
  21. 21.
    Kukita, A., Kukita, T., Shin, J. H., and Kohashi, O. (1993) Induction of mononuclear precursor cells with osteoclastic phenotypes in a rat bone marrow culture system depleted of stromal cells. Biochem. Biophys. Res. Commun. 196, 1389–1389.CrossRefGoogle Scholar
  22. 22.
    Udagawa, N., Takahashi, N., Akatsu, T., Sasaki, T., Yamaguchi, A., Kodama, H., et al. (1989) The bone marrowderived stromal cell lines MC3T3-G2/PA6 and ST2 support osteoclast-like cell differentiation in cocultures with mouse spleen cells. Endocrinology 125, 1805–1813.PubMedCrossRefGoogle Scholar
  23. 23.
    Chambers, T. J., Owens, J. M., Hattersley, G., Jat, P. S., and Noble, M. D. (1993) Generation of osteoclast-inductive and osteoclastogenic cell lines from the H-2KbtsA58 transgenic mouse. Proc. Natl. Acad. Sci. USA 90, 5578–5582.PubMedCrossRefGoogle Scholar
  24. 24.
    Hill, P. A., Reynolds, J. J., and Meikle, M. C. (1995) Osteoblasts mediate insulin-like growth factor-I and -II stimulated osteoclast formation and function. Endocrinology 136, 124–131.PubMedCrossRefGoogle Scholar
  25. 25.
    Shevde, N., Anklesaria, P., Greenberger, J. S., Bleiberg, I., and Glowacki, J. (1994) Stromal cell-mediated stimulation of osteoclastogenesis. Proc. Soc. Exp. Biol. Med. 205, 306–315.PubMedGoogle Scholar
  26. 26.
    Takahashi, S., Reddy, S. V., Dallas, M., Devlin, R., Chou, J. Y., and Roodman, G. D. (1995) Development and characterization of a human marrow stromal cell line that enhances osteoclast-like cell formation. Endocrinology 136, 1441–1449.PubMedCrossRefGoogle Scholar
  27. 27.
    Quinn, J. M., Horwood, N. J., Elliott, J., Gillespie, M. T., and Martin, T. J. (2000) Fibroblastic stromal cells express receptor activator of NF kappa B ligand and support osteoclast differentiation. J. Bone Miner. Res. 15, 1459–1466.PubMedCrossRefGoogle Scholar
  28. 28.
    Franzoso, G., Carlson, L., Xing, L., Poljak, L., Shores, E. W., Brown, K. D., et al. (1997) Requirement for NF-kappaB in osteoclast and B-cell development. Genes Dev. 11, 3482–3496.PubMedCrossRefGoogle Scholar
  29. 29.
    Xing, L., Bushnell, T. P., Carlson, L., Tai, Z., Tondravi, M., Siebenlist, U., et al. (2002) NF-kappaB p50 and p52 expression is not required for RANK expressing osteoclast progenitor formation but is essential for RANK and cytokine mediated osteoclastogenesis. J. Bone Miner. Res. 17, 1200–1210.PubMedCrossRefGoogle Scholar
  30. 30.
    Tondravi, M. M., McKercher, S. R., Anderson, K., Erdmann, J. M., Quiroz, M., Maki, R., et al. (1997) Osteopetrosis in mice lacking hematopoietic transcription factor PU.1. Nature 386, 81–84.PubMedCrossRefGoogle Scholar
  31. 31.
    Luchin, A., Suchting, S., Merson, T., Rosol, T. J., Hume, D. A., Cassady, A. I., et al. (2001) Genetic and physical interactions between micropththalmia transcription factor and PU.1 are necessary for osteoclast gene expression and differentiation. J. Biol. Chem. 276, 36703–36710.PubMedCrossRefGoogle Scholar
  32. 32.
    Grigoriadis, A. E., Wang, Z. Q., Cecchini, M. G., Hofstetter, W., Felix, R., Fleisch, H. A., et al. (1994) c-fos: a key regulator of osteoclast-macrophage lineage determination and bone remodeling. Science 266, 443–448.PubMedCrossRefGoogle Scholar
  33. 33.
    Hoyland, J. and Sharpe, P. T. (1994): Upregulation of c-fos proto-oncogene expression in pagetic osteoclasts. J. Bone Miner. Res. 9. 1191–1194.PubMedCrossRefGoogle Scholar
  34. 34.
    Owens, J. M., Matsuo, K., Nicholson, G. C., Wagner, E. F., and Chambers, T. J. (1999) Fra-I stimulates osteoclastic differentiation in osteoclast macrophage precursor cell lines. J. Cell Physiol. 179, 170–178.PubMedCrossRefGoogle Scholar
  35. 35.
    Fleischmann, A., Hafezi, F., Elliott, C., Reme, C. E., Ruther, U., and Wagner, E. F. (2000) Fra-1 replaces c-fos dependent functions in mice. Genes Dev. 14, 2695–2700.PubMedCrossRefGoogle Scholar
  36. 36.
    Matsuo, K., Jochum, W., Owens, J. M., Chambers, T. J., and Wagner, E. F. (1999) Function of Fos proteins in bone cell differentiation. Bone 25, 141.PubMedCrossRefGoogle Scholar
  37. 37.
    Matsuo, K., Owens, J. M., Tonko, M., Elliott, C., Chambers, T. J., and Wagner, E. F. (2000) Fosl 1 is a transcriptional target of cfos during osteoclast differentiation. Nat. Genet. 24, 184–187.PubMedCrossRefGoogle Scholar
  38. 38.
    Udagawa, N., Chan, J., Wada, S., Findlay, D. M., Hamilton, J. A., and Martin, T. J. (1996) c-fos antisense DNA inhibits proliferation of osteoclast progenitors in osteoclast development but not macrophage differentiation in vitro. Bone 18, 511–516.PubMedCrossRefGoogle Scholar
  39. 39.
    Soriano, P., Montgomery, C., Geske, R., and Bradley, A. (1991) Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in mice. Cell 64, 693–702.PubMedCrossRefGoogle Scholar
  40. 40.
    Boyce, B. F., Yoneda, T., Lowe, C., Soriano, P., and Mundy, G. R. (1992) Requirement of pp60c-src expression for osteoclasts to form ruffled borders and resorb bone in mice. J. Clin. Invest. 90, 1622–1627.PubMedCrossRefGoogle Scholar
  41. 41.
    Lowe, C., Yoneda, T., Boyce, B. F., Chen, H., Mundy, G. R., and Soriano, P. (1993) Osteopetrosis in src-deficient mice is due to an autonomous defect of osteoclasts. Proc. Natl. Acad. Sci. USA 90, 4485–4489.PubMedCrossRefGoogle Scholar
  42. 42.
    Schwartzberg, P. L., Xing, L., Hoffmann, O., Lowell, C. A., Garrett, L., Boyce, B. F., et al. (1997) Rescue of osteoclast function by transgenic expression of kinase-deficient src in src-1- mutant mice. Genes Dev. 11, 2835–2844.PubMedCrossRefGoogle Scholar
  43. 43.
    Abu-Amer, Y., Ross, F. P., Schlesinger, P., Tondravi, M. M., and Teitelbaum, S. L. (1997) Substrate recognition by osteoclast precursors induces c-src/microtubule association. J. Cell Biol. 137, 247–258.PubMedCrossRefGoogle Scholar
  44. 44.
    Tanaka, S., Amling, M., Neff, L., Peyman, A., Uhlmann, E., Levy, J. B., and Baron, R. (1996) C-cbl is downstream of -src in a signaling pathway necessary for bone resorption. Nature 383, 528–531.PubMedCrossRefGoogle Scholar
  45. 45.
    Sanjay, A., Houghton, A., Neff, L., DiDomenico, E., Bardelay, C., Antoine, E., et al. (2001) Cbl associates with Pyk2 and Src to regulate Src kinase activity, alpha(v) beta(3) integrin mediated signaling, cell adhesion and osteoclast motility. J. Cell Biol. 152, 181–195.PubMedCrossRefGoogle Scholar
  46. 46.
    Inoue, D., Santiago, P., Horne, W. C., and Baron, R. (1997) Identification of an osteoclast transcription factor that binds to the human T cell leukemia virus type I-long terminal repeat enhancer element. J. Biol. Chem. 272, 25386–25393.PubMedCrossRefGoogle Scholar
  47. 47.
    Mansky, K. C., Sankar, U., Han, J., and Ostrowski, M. C. (2002) Micropththalmia transcription factor (MITF) is a target of the p38 MAPK pathway in response to receptor activator of NF-kB ligand signaling. J. Biol. Chem. 277, 11077–11083.PubMedCrossRefGoogle Scholar
  48. 48.
    Weilbaecher, K. N., Motyckova, G., Huber, W. E., Takemoto, C. M., Hemesath, T. J., Xu, Y., et al. (2001) Linkage of M-CSF signaling to Mitf, TFE3, and the osteoclast defect in Mitf(mi/mi) mice. Mol. Cell. 8, 749–758.PubMedCrossRefGoogle Scholar
  49. 49.
    Mansky, K. C., Sulzbacher, S., Purdom, G., Nelsen, L., Hume, D. A., Rehli, M., et al. (2002) The micropthalmia transcription factor and the related helix-loop-helix zipper factors TFE3 and TFE-C collaborate to activate the tartrate resistant acid phosphatase promoter. J. Leukoc. Biol. 71, 304–310.PubMedGoogle Scholar
  50. 50.
    Battaglino, R., Kim, D., Fu, J., Vaage, B., Fu, X. Y., and Stashenko, P. (2002) c-myc is required for osteoclast differentiation. J. Bone Miner. Res. 17, 763–773.PubMedCrossRefGoogle Scholar
  51. 51.
    Anderson, B. M., Maraskovsky, E., Billingsley, W. L., Dougall, W. C., Tometsko, M. E., Roux, E. R., et al. (1997) A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function. Nature 390, 175–179.PubMedCrossRefGoogle Scholar
  52. 52.
    Wong, B. R., Josien, R., Lee, S. Y., Sauter, B., Li, H. L., Steinman, R. M., et al. (1997) TRANCE (tumor necrosis factor [TNH-related activation-induced cytokine), a new TNF family member predominantly expressed in T cells, is a dendritic cell-specific survival factor. J. Exp. Med. 186, 2075–2080.PubMedCrossRefGoogle Scholar
  53. 53.
    Yasuda, H., Shima, N., Nakagawa, N., Mochizuki, S., Yano, K., Fujise, N., et al. (1998) Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): A mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro. Endrocrinology 139, 1329–1337.CrossRefGoogle Scholar
  54. 54.
    Yasuda, H., Shima, N., Nakagawa, N., Yamaguchi, K., Kinosaki, M., Mochizuki, S., et al. (1998) Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc. Natl. Acad. Sci. USA 95, 3597–3602.PubMedCrossRefGoogle Scholar
  55. 55.
    Lacey, D. L., Tan, H. L., Lu, J., Kaugman, S., Van, G., Qiu, W., et al. (2000) Osteoprotegerin ligand modulates murine osteoclast survival in vitro and in vivo. Am. J. Pathol. 157, 35–48.CrossRefGoogle Scholar
  56. 56.
    Kojima, H., Nemoto, A., Uemura, T., Honma, R., Ogura, M., and Liu, Y. (2001) rDrak 1 , a novel kinase related to apoptosis, is strongly expressed in active osteoclasts and induces apoptosis. J. Biol. Chem. 276, 19238–19243.PubMedCrossRefGoogle Scholar
  57. 57.
    Felix, R., Cecchini, M. C., and Fleisch, H. (1990) Macrophage colony-stimulating factor restores in vivo bone resorption in the op/op osteopetrotic mouse. Endocrinology 127, 2592–2594.PubMedCrossRefGoogle Scholar
  58. 58.
    Yoshida, H., Hayashi, S., Kunisada, T., Ogawa, M., Nishikawa, S., Okumura, H., et al. (1990) The murine mutation osteopetrosis is in the coding region of the macrophage colony-stimulating factor gene. Nature 345, 442–444.PubMedCrossRefGoogle Scholar
  59. 59.
    Tanaka, S., Takahashi, N., Udagawa, N., Tamura, T., Akatsu, T., Stanley, E. R., et al. (1993) Macrophage colonystimulating factor is indispensable for both proliferation and differentiation of osteoclast progenitors. J. Clin. Invest. 91, 257–263.PubMedCrossRefGoogle Scholar
  60. 60.
    Takahashi, N., Udagawa, N., Akatsu, T., Tanaka, H., Isogai, Y., and Suda, T. (1991) Deficiency of osteoclasts in osteopetrotic mice is due to a defect in the local microenvironment provided by osteoblastic cells. Endocrinology 128, 1792–1796.PubMedCrossRefGoogle Scholar
  61. 61.
    Halasy, J. and Hofstetter, W. (1998) Expression of colony-stimulating factor-1 (CSF-1) during the formation of osteoclasts in vivo. J. Bone Miner. Res. 13, 1267–1274.CrossRefGoogle Scholar
  62. 62.
    Yamane, T., Kunisada, T., Yamazaki, H., Era, T., Nakano, T., and Hayashi, S. I. (1997) Development of osteoclasts from embryonic stem cells through a pathway that is c-fms but not c-kit dependent. Blood 90, 3516–3523.PubMedGoogle Scholar
  63. 63.
    Fan, X., Biskobing, D. M., Fan, D., Hofstetter, W., and Rubin, J. (1997) Macrophage colony stimulating factor downregulates M-CSF receptor expression and entity of progenitors into the osteoclast lineage. J. Bone Miner. Res. 12, 1387–1395.PubMedCrossRefGoogle Scholar
  64. 64.
    Nilsson, S. K., Lieschke, G. J., Garcia-Wijnen, C. C., Williams, B., Tzelepis, D., Hodgson, G., et al. (1995) Granulocyte-macrophage colony-stimulating factor is not responsible for the correction of hematopoietic deficiencies in the maturing op/op mouse. Blood 86, 66–72.PubMedGoogle Scholar
  65. 65.
    Lean, J. M., Fuller, K., and Chambers, T. J. (2001) FLT3 ligand can substitute for macrophage colony stimulating factor in support of osteoclast differentiation and function. Blood 98, 2707–2713.PubMedCrossRefGoogle Scholar
  66. 66.
    Simonet, W. S., Lacey, D. L., Dunstan, C. R., Kelley, M., et al. (1997) Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 89, 309–319.PubMedCrossRefGoogle Scholar
  67. 67.
    Tsurukai, T., Udagawa, N., Masuzaki, K., Takahashi, N., and Suda, T. (2000) Roles of macrophage-colony stimulating factor and osteoclast differentiation factor in osteoclastogenesis. J. Bone Miner. Res. 18, 177–184.CrossRefGoogle Scholar
  68. 68.
    Gori, F., Hofbauer, L. C., Dunstan, C. R., Spelsberg, T. C., Khosla, S., and Riggs, B. L. (2000) The expression of osteoprotegerin and RANK ligand and the support of osteoclast formation by stromal-osteoblast lineage cells is developmentally regulated. Endocrinology 141, 4768–4776.PubMedCrossRefGoogle Scholar
  69. 69.
    Hofbauer, L. C., Gori, F., Riggs, B. L., Lacey, D. L., Dunstan, C. R., Spelsberg, T. C., et al. (1999) Stimulation of osteoprotegerin ligand and inhibition of osteoprotegerin production by glucocorticoids in human osteoblastic lineage cells: potential paracrine mechanisms of glucocorticoid induced osteoporosis. Endocrinology 140, 4382–4389.PubMedCrossRefGoogle Scholar
  70. 70.
    Horwood, N. J., Elliott, J., Martin, T. J., and Gillespie, M. T. (1998) Osteotropic agents regulate the expression of osteoclast differentiation factor and osteoprotegerin in osteoblastic stromal cells. Endocrinology 139, 4743–4746.PubMedCrossRefGoogle Scholar
  71. 71.
    Thirunavukkarasu, K., Miles, R. R., Halladay, D. L., Yang, X., Galvin, R. J., Chandrasekhar, S., et al. (2001) Stimulation of osteoprotegerin (OPG) gene expression by transforming growth factor-beta (TGF-beta). Mapping of the OPG promoter region that mediates TGF beta effects. J. Biol. Chem. 276, 3641–3650.CrossRefGoogle Scholar
  72. 72.
    Pfeilschifter, J., Chenu, C., Bird, A., Mundy, G. R., and Roodman, G. D. (1989) Interleukin-1 and tumor necrosis factor stimulate the formation of human osteoclast-like cells in vitro. J. Bone Miner. Res. 4, 113–118.PubMedCrossRefGoogle Scholar
  73. 73.
    Uy, H. L., Mundy, G. R., Boyce, B. F., Story, B. M., Dunstan, C. R., Yin, J. J., et al. (1997) Tumor necrosis factor enhances parathyroid hormone-related protein-induced hypercalcemia and bone resorption without inhibiting bone formation in vivo. Cancer Res. 573, 3194–3199.Google Scholar
  74. 74.
    Pacifici, R. (1996) Estrogen, cytokines and pathogenesis of postmenopausal osteoporosis. J. Bone Miner. Res. 11, 1043–1051.PubMedCrossRefGoogle Scholar
  75. 75.
    Kobayashi, K., Takahashi, N., Jimi, E., Udagawa, N., Takami, M., Kotake, S., et al. (2000) Tumor necrosis factor alpha stimulates osteoclast differentiation by a mechanism independent of the ODF/RANKL-RANK interaction. J. Exp. Med. 191, 275–286.PubMedCrossRefGoogle Scholar
  76. 76.
    Lam, J., Takeshita, S., Barker, J. E., Kanagawa, O., Ross, F. P., and Teitelbaum, S. L. (2000) TNF alpha induces osteoclastogenesis by direct stimulation of macrophages exposed to permissive levels of RANK ligand. J. Clin. Invest. 106, 1481–1488.PubMedCrossRefGoogle Scholar
  77. 77.
    Boyce, B. F., Aufdemorte, T. B., Garrett, I. R., Yates, A. J., and Mundy, G. R. (1989) Effects of interleukin-1 on bone turnover in normal mice. Endocrinology 125, 1142–1150.PubMedCrossRefGoogle Scholar
  78. 78.
    Uy, H. L., Guise, T. A., De La Mata, J., Taylor, S. D., Story, B. M., Dallas, M. R., et al. (1995) Effects of parathyroid hormone-related protein and PTH on osteoclasts and osteoclast precursors in vivo. Endocrinology 136, 3207–3212.PubMedCrossRefGoogle Scholar
  79. 79.
    Van’t Hof, R. J., Armour, K. J., Smith, L. M., Armour, K. E., Wei, X. Q., Liew, F. Y., et al. (2000) Requirement of the inducible nitric oxide synthase pathway for IL-1 induced osteoclastic bone resorption. Proc. Natl. Acad. Sci. USA 97, 7993–7998.PubMedCrossRefGoogle Scholar
  80. 80.
    Fox, S. W., Fuller, K., and Chambers, T. J. (2000) Activation of osteoclasts by interleukin-1: divergent responsiveness in osteoclasts formed in vivo and in vitro. J. Cell Physiol. 184, 334–340.PubMedCrossRefGoogle Scholar
  81. 81.
    Riancho, J. A., Zarrabeitia, M. T., and Gonzalez-Macias, J. (1993) Interleukin-4 modulates osteoclast differentiation and inhibits the formation of resorption pits in mouse osteoclast cultures. Biochem. Biophys. Res. Commun. 196, 678–685.PubMedCrossRefGoogle Scholar
  82. 82.
    Nakano, Y., Watanabe, K., Morimoto, I., Okada, Y., Ura, K., Sato, K., et al. (1994) Interleukin-4 inhibits spontaneous and parathyroid hormone-related protein-stimulated osteoclast formation in mice. J. Bone Miner. Res. 9, 1533–1539.PubMedCrossRefGoogle Scholar
  83. 83.
    Lewis, D. B., Liggitt, H. D., Effmann, E. L., Motley, S. T., Teitelbaum, S. L., Jepsen, K. J., et al. (1993) Osteoporosis induced in mice by overproduction of interleukin 4. Proc. Natl. Acad. Sci. USA 90, 11618–11622.PubMedCrossRefGoogle Scholar
  84. 84.
    Abu-Amer, Y. (2001) IL-4 abrogates osteoclastogenesis through STAT6 dependent inhibition of NF-κB. J. Clin Invest. 107, 1375–1385.PubMedCrossRefGoogle Scholar
  85. 85.
    Roodman, G. D. (1996) Advances in bone biology: the osteoclast. Endocr. Rev. 17, 308–332.PubMedGoogle Scholar
  86. 86.
    Kurihara, N., Bertolini, D., Suda, T., Akiyama, Y., and Roodman, G. D. (1990) IL-6 stimulates osteoclast-like multinucleated cell formation in long-term human marrow cultures by inducing IL-1 release. J. Immunol. 144, 4226–4230.PubMedGoogle Scholar
  87. 87.
    Ohsaki, Y., Takahashi, S., Scarcez, T., Demulder, A., Nishihara, T., Williams, R., et al. (1992) Evidence for an autocrine/paracrine role for IL-6 in bone resorption by giant cell tumors of bone. Endocrinology 131, 2229–2234.PubMedCrossRefGoogle Scholar
  88. 88.
    Reddy, S. V., Takahashi, S., Dallas, M., Williams, R. E., Neckers, L., and Roodman, G. D. (1994) IL-6 antisense deoxyoligonucleotides inhibit bone resorption by giant cells from human giant cell tumors of bone. J. Bone Miner. Res. 9, 753–757.PubMedCrossRefGoogle Scholar
  89. 89.
    Devlin, R. D., Reddy, S. V., Savino, R., Ciliberto, G., and Roodman, G. D. (1998) IL-6 mediates the effects of IL-1 or TNF, but not PTHrP or 1,25(OH)2D3 on osteoclast-like cell formation in normal human bone marrow culture. J. Bone Miner. Res. 13, 393–399.PubMedCrossRefGoogle Scholar
  90. 90.
    Udagawa, N., Takahashi, N., Katagiri, T., Tamura, T., Wada, S., Findlay, D. M., et al. (1995) Interleukin-6 induction of osteoclast differentiation depends on IL-6 receptors expressed on osteoblastic cells but not on osteoclast progenitors. J. Exp. Med. 182, 1461–1468.PubMedCrossRefGoogle Scholar
  91. 91.
    Holt, I., Davie, M. W., Braidman, I. P., and Marshall, M. J. (1994) Interleukin-6 does not mediate the stimulation by prostaglandin E2, parathyroid hormone, or 1,25 dihydroxyvitamin D3 of osteoclast differentiation and bone resorption in neonatal mouse parietal bones. Calcif. Tissue Int. 52, 114–119.CrossRefGoogle Scholar
  92. 92.
    Passeri, G., Girasole, G., Jilka, R. L., and Manolagas, S. C. (1993) Increased interleukin-6 production by murine bone marrow and bone cells after estrogen withdrawal. Endocrinology 133, 822–828.PubMedCrossRefGoogle Scholar
  93. 93.
    Han, J. H., Choi, S. J., Kurihara, N., Koide, M., Oba, Y., and Roodman, G. D. (2001) Macrophage inflammatory protein-1 alpha is an osteoclastogenic factor in myeloma that is independent of receptor activator of nuclear factor kappaB ligand. Blood 97, 3349–3353.PubMedCrossRefGoogle Scholar
  94. 94.
    Paul, S. R., Bennett, F., Calvetti, J. A., Kelleher, K., Wood, C. R., O’Hara, R. M., et al. (1990) Molecular cloning of a cDNA encoding interleukin-11, a stromal cell-derived lymphopoietic and hematopoietic cytokine. Proc. Natl. Acad. Sri USA R7. 7512–7516.CrossRefGoogle Scholar
  95. 95.
    Girasole, G., Passeri, G., Jilka, R. L., and Manolagas, S. C. (1994) Interleukin 11: a new cytokine critical for osteoclast development. J. Clin. Invest. 93, 1516–1524.PubMedCrossRefGoogle Scholar
  96. 96.
    Galvin, R. J., Bryan, P., Horn, J. W., Rippy, M. K., and Thomas, J. E. (1996) Development and characterization of a Porcine model to study osteoclast differentiation and activity. Bone 19, 271–279.PubMedCrossRefGoogle Scholar
  97. 97.
    Musashi, M., Yang, Y. C., Paul, S. R., Clark, S. C., Sudo, T., and Ogawa, M. (1991) Direct and synergistic effects of interleukin-11 on muirine hemonoiesis in culture. Proc. Natl. Acad. Sci. USA 88. 765–769.PubMedCrossRefGoogle Scholar
  98. 98.
    Chenu, C., Pfeilschifter, J., Mundy, G. R., and Roodman, G. D. (1988) Transforming growth factor beta inhibits formation of osteoclast-like cells in long-term human marrow cultures. Proc. Natl. Acad. Sci. USA 85, 5683–5687.PubMedCrossRefGoogle Scholar
  99. 99.
    Yan, T., Riggs, B. L., Boyle, W. J., and Khosla, S. (2001) Regulation of osteoclastogenesis and RANK expression by TGE-betal. J. Cell Biochem. 4, 1041–1049.Google Scholar
  100. 100.
    Gowen, M. and Mundy, G. R. (1986) Actions of recombinant interleukin-1, interleukin-2, and interferon gamma on bone resorption in vitro. J. Immunol. 136, 2478–2482.PubMedGoogle Scholar
  101. 101.
    Takahashi, N., Mundy, G. R., and Roodman, G. D. (1986) Recombinant human interferon-y inhibits formation of human osteoclast-like cells. J. Immunol. 137, 3544–3549.PubMedGoogle Scholar
  102. 102.
    Kurihara, N. and Roodman, G. D. (1990) Interferons-a and -y inhibit interleukin-113-stimulated osteoclast-like cell formation in long-term human marrow cultures. J. Interferon Res. 10, 541–547.PubMedCrossRefGoogle Scholar
  103. 103.
    Takayanagi, H., Ogasawara, K., Hida, S., Chiba, T., Murata, S., Sato, K., et al. (2000) T-cell-mediated regulation of osteoclastogenesis by signaling cross-talk between RANKL and IFN-y. Nature 408, 600–605.PubMedCrossRefGoogle Scholar
  104. 104.
    Fox, S. W. and Chambers, T. J. (2000) Interferon-y directly inhibits TRANCE induced osteoclastogenesis. Biochem. Biophys. Res. Commun. 276, 868–872.PubMedCrossRefGoogle Scholar
  105. 105.
    van’t Hof, R. J. and Ralston, S. H. (2001) Nitric oxide and bone. Immunology 103, 255–261.CrossRefGoogle Scholar
  106. 106.
    Takayanagi, H., Kim, S., Matsuo, K., Suzuki, H., Suzuki, T., Sato, K., et al. (2002) RANKL maintains bone homeostasis through c-Fos dependent induction of interferon-β3. Nature 416, 744–749.PubMedCrossRefGoogle Scholar
  107. 107.
    Kurihara, N., Chenu, C., Civin, C. I., and Roodman, G. D. (1990) Identification of committed mononuclear precursors for osteoclast-like cells formed in long-term marrow cultures. Endocrinology 126, 2733–2741.PubMedCrossRefGoogle Scholar
  108. 108.
    Menaa, C., Barsony, J., Reddy, S. V., Cornish, J., Cundy, T., and Roodman, G. D. (2000) 1,25 dihydroxyvitamin D3 hypersensitivity of osteoclast precursors from patients with Paget’s disease, J. Bone Miner. Res. 15, 228–236.PubMedCrossRefGoogle Scholar
  109. 109.
    Feyen, J. H., Elford, P., Di Padova, F. E., and Trechsel, U. (1989) Interleukin-6 is produced by bone and modulated by parathyroid hormone. J. Bone Miner. Res. 4, 633–638.PubMedCrossRefGoogle Scholar
  110. 110.
    Abe, J., Takita, Y., Nakano, T., Miyaura, C., Suda, T., and Nishii, Y. (1989) A synthetic analogue of vitamin D3,22oxa-1 alpha, 25-dihydroxyvitamin D3, is a potent modulator of in vivo immunoregulating activity without inducing hypercalcemia in mice. Endocrinology 124, 2645–2647.PubMedCrossRefGoogle Scholar
  111. 111.
    Woods, C., Domenget, C., Solari, F., Gandrillon, O., Lazarides, E., and Judic, P. (1995) Antagonistic role of vitamin D3 and retinoic acid on the differentiation of chicken hematopoietic macrophages into osteoclast precursor cells. Endocrinology 136, 85–95.PubMedCrossRefGoogle Scholar
  112. 112.
    Chirgwin, J. M. and Guise, T. (2000) Molecular mechanisms of tumor-bone interactions in osteolytic metastasis. Crit. Rev. Eukaryot. Gene Exp. 10, 159–78.Google Scholar
  113. 113.
    Rodan, G. A. and Martin, T. J. (1981) Role of osteoblasts in hormonal control of bone resorption: a hypothesis. Calcif. Tissue Int. 33, 349–351.PubMedCrossRefGoogle Scholar
  114. 114.
    McSheehy, P. M. J. and Chambers, T. J. (1986) Osteoblastic cells mediate osteoclastic responsiveness to parathyroid hormone. Endocrinology 118, 824–828.PubMedCrossRefGoogle Scholar
  115. 115.
    Greenfield, E. M., Horowitz, M. C., and Lavish, S. A. (1996) Stimulation by parathyroid hormone of interleukin-6 and leukemia inhibitory factor expression in osteoblasts is an immediate-early gene response induced by cAMP signal transduction. J. Biol. Chem. 271, 10984–10989.PubMedCrossRefGoogle Scholar
  116. 116.
    Kurihara, N., Civin, C., and Roodman, G. D. (1991) Osteotropic factor responsiveness of highly purified populations of early and late precursors for human multinucleated cells expressing the osteoclast phenotype. J. Bone Miner. Res. 6, 257–261.PubMedCrossRefGoogle Scholar
  117. 117.
    Agarwala, N. and Gay, C. V. (1992) Specific binding of parathyroid hormone to living osteoclasts. J. Bone Miner. Res. 7, 531–539.PubMedCrossRefGoogle Scholar
  118. 118.
    Teti, A., Rizzoli, R., and Zambonin-Zallone, A. (1991) A parathyroid hormone binding to cultured avian osteoclasts. Biochem. Biophvs. Res. Commun. 174, 1217–1222.CrossRefGoogle Scholar
  119. 119.
    Hakeda, Y., Hiura, K., Sato, T., Olazaki, R., Matsumoto, T., Ogata, E., et al. (1989) Existence of parathyroid hormone binding sites on murine hemopoietic blast cells. Biochem. Biophys. Res. Commun. 163, 1481–1486.PubMedCrossRefGoogle Scholar
  120. 120.
    Orlandini, S. Z., Formigli, L., Benvenuti, S., Lasagni, L., Franchi, A., Masi, L., et al. (1995) Functional and structural interactions between osteoblastic and preosteoclastic cells in vitro. Cell Tissue Res. 281, 33–42.PubMedCrossRefGoogle Scholar
  121. 121.
    Tong, H., Lin, H., Wang, H., Sakai, D., and Minkin, C. (1995) Osteoclasts respond to parathyroid hormone and express mRNA for its receptor. J. Bone Miner. Res. 10, 5322.Google Scholar
  122. 122.
    Kartsogiannis, V., Udagawa, N., Martin, T. J., Moseley, J. M., and Zhou, H. (1998) Localization of parathyroid hormone-related protein in osteoclasts by in situ hybridization and immunohistochemistry. Bone 22, 189–194.PubMedCrossRefGoogle Scholar
  123. 123.
    Lee, S. K., Goldring, S. R., and Lorenzo, J. A. (1995) Expression of the calcitonin receptor in bone marrow cell cultures and in bone: a specific marker of the differentiated osteoclast that is regulated by calcitonin. Endocrinology 136, 4572–4581.PubMedCrossRefGoogle Scholar
  124. 124.
    Gorn, A. H., Rudolph, S. M., Flannery, M. R., Morton, C. C., Weremowicz, S., Wang, T. Z., et al. (1995) Expression of two human skeletal calcitonin receptor isoforms cloned from a giant cell tumor of bone. The first intracellular domain modulates ligand binding and signal transduction. J. Clin. Invest. 95, 2680–2691.PubMedCrossRefGoogle Scholar
  125. 125.
    Shevde, N. K., Bendixen, A. C., Dienger, K. M., and Pike, J. M. (2000) Estrogens suppress RANK ligand-induced osteoclast differentiation via a stromal cell independent mechanism involving c-Jun repression. Proc. Natl. Acad. Sci. USA 97, 7829–7834.PubMedCrossRefGoogle Scholar
  126. 126.
    Viereck, V., Grundker, C., Blaschke, S., Siggelkow, H., Emons, G., and Hofbauer, L. C. (2002) Phytoestrogen genistein stimulates the production of osteoprotegerin by human trabecular osteoblasts. J. Cell Biochemn. 84, 725–735.CrossRefGoogle Scholar
  127. 127.
    Szulc, P., Hofbauer, L. C., Heufelder, A. E., Roth, S., and Delmas, P. D. (2001) Osteoprotegerin serum levels in men: correlation with age, estrogen and testosterone status. J. Clin. Endocrinol. Metab. 86, 3162–3165.PubMedCrossRefGoogle Scholar
  128. 128.
    Takahashi, N., Yamana, H., Yoshiki, S., Roodman, G. D., Mundy, G. R., Jones, S. J., et al. (1988) Osteoclast-like cell formation and its regulation by osteotropic hormones in mouse bone marrow cultures. Endocrinology 122, 1373–1382.PubMedCrossRefGoogle Scholar
  129. 129.
    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-ββ. J. Bone Miner. Res. 5,677–681.PubMedCrossRefGoogle Scholar
  130. 130.
    Quinn, J. M. W., Sabokbar, A., Denne, M., de Vernejoul, M. C., McGee, J. O. D., and Athanasou, N. A. (1997) Inhibitory and stimulatory effects of prostaglandins on osteoclast differentiation. Calcif Tissue Int. 60, 63–70.PubMedCrossRefGoogle Scholar
  131. 131.
    Roux, S., Pichaud, F., Quinn, J., Lalande, A., Morieux, C., Jullienne, A., et al. (1997) Effects of prostaglandins on human hematopoietic osteoclast precursors. Endocrinology 138, 1476–1482.PubMedCrossRefGoogle Scholar
  132. 132.
    Tashjian, A. H., Voelkel, E. F., Lazzaro, M., Goad, D., Bosma, T., and Levine, L. (1985) Alpha and beta transforming growth factors stimulate prostaglandin production and bone resorption in cultured mouse calvaria. Proc. Natl. Acad. Sci. USA 82, 4535–4538.PubMedCrossRefGoogle Scholar
  133. 133.
    Wani, M. R., Fuller, K., Kim, N. S., Choi, Y., and Chambers, T. (1999) Prostaglandin E2 cooperates with TRANCE in osteoclast induction from hemopoietic precursors: synergistic activation of differentiation, cell spreading, and fusion. Endocrinology 140, 1927–1935.PubMedCrossRefGoogle Scholar
  134. 134.
    Gallwitz, W. E., Mundy, G. R., Lee, C. H., Qiao, M., Roodman, G. D., Raftery, M., et al. (1993) 5-Lipoxygenase metabolites of arachidonic acid stimulate isolated osteoclasts to resorb calcified matrices. J. Biol. Chem. 268, 10087–10094.PubMedGoogle Scholar
  135. 135.
    Franchi-Miller, C. and Saffar, J. L. (1995) The 5-lipoxygenase inhibitor BWA4C impairs osteoclastic resorption in a synchronized model of bone remodeling. Bone 17, 185–191.PubMedCrossRefGoogle Scholar
  136. 136.
    Garcia, C., Boyce, B. F., Gilles, J., Dallas, M., Qiao, M., Mundy, G. R., et al. (1996) Leukotriene B4 stimulates osteoclastic bone resorption both in vitro and in vivo. J. Bone Miner. Res. 11, 1619–1627.PubMedCrossRefGoogle Scholar
  137. 137.
    Takami, M., Woo, J. T., Takahashi, N., Suda, T., and Nagai, K. (1997) Ca2+-ATPase inhibitors and Ca2+ ionophore induce osteoclast-like cell formation in the cocultures of mouse bone marrow cells and calvarial cells. Biochem. Biovhvs. Res. Commun. 237, 111–115.CrossRefGoogle Scholar
  138. 138.
    Takami, A., Takahashi, N., Udagawa, N., Miyaura, C., Suda, K., Woo, J. T., et al. (2000) Intracellular calcium and protein kinase C mediate expression of receptor activator of nuclear factor-kappa B ligand and osteoprotegerin in osteoblasts. Endocrinology 141, 4711–4719.PubMedCrossRefGoogle Scholar
  139. 139.
    Biskobing, D. M., Fan, D., and Rubin, J. (1997) Induction of carbonic anhydrase II expression in osteoclast progenitors reauires physical contact with stromal cells. Endocrino/o g y 138, 4852–4857.CrossRefGoogle Scholar
  140. 140.
    Moonga, B. S. and Dempster, D. W. (1995) Zinc is a potent inhibitor of osteoclastic bone resorption in vitro. J. Bone Miner. Res. 10, 453–457.PubMedCrossRefGoogle Scholar
  141. 141.
    Suzuki, Y., Morita, I., Yamane, Y., and Murota, S. (1990) Preventive effect of zinc against cadmium-induced bone resorption. Toxicology 62, 27–34.PubMedCrossRefGoogle Scholar
  142. 142.
    Kishi, S. and Yamaguchi, M. (1994) The inhibitory effects of zinc compounds on osteoclast-like cell formation in mouse marrow cultures. Biochem. Pharmacol. 48, 1225–1230.PubMedCrossRefGoogle Scholar
  143. 143.
    Kishi, S. and Yamaguchi, M. (1997) Characterization of zinc effect to inhibit osteoclast-like cell formation in mouse bone marrow cultures: Interactions with dexamethasone. Mol. Cell. Biochem. 166, 145–151.PubMedCrossRefGoogle Scholar
  144. 144.
    Holloway, W. R., Collier, F. M., Herbst, R. E., Hodge, J. M., and Nicholson, G. C. (1996) Osteoblast-mediated effects of zinc on isolated rat osteoclasts: inhibition of bone resorption and enhancement of osteoclast number. Bone 19. 137–142.PubMedCrossRefGoogle Scholar
  145. 145.
    Wilson, A. K., Cerny, E. A., Smith, B. D., Wagh, A., and Bhattacharyya, M. H. (1996) Effect of cadmium on osteoclast formation and activity in vitro. Toxicol. Appl. Pharm. 140, 451–460.CrossRefGoogle Scholar
  146. 146.
    Notoya, K., Yoshida, K., Taketomi, S., Yamazaki, I., and Kumegawa, M. (1993) Inhibitory effect of ipriflavone on osteoclast mediated bone resorption and new osteoclast formation in long-term cultures of mouse unfractionated bone cells. Calc. Tissue Int. 53, 206–209.CrossRefGoogle Scholar
  147. 147.
    Miyauchi, A., Notoya, K., Taketomi, S., Takagi, Y., Fujii, Y., Jinnai, K., et al. (1996) Novel ipriflavone receptors coupled to calcium influx regulate osteoclast differentiation and function. Endocrinology 137, 3544–3550.PubMedCrossRefGoogle Scholar
  148. 148.
    Shibutani, T. and Heersche, J. N. (1993) Effect of medium pH on osteoclast activity and osteoclast formation in cultures of dispersed rabbit osteoclasts. J. Bone Miner. Res. 8,331–336.PubMedCrossRefGoogle Scholar
  149. 149.
    Arnett, T. R. and Dempster, D. W. (1990) Protons and osteoclasts. J. Bone Miner. Res. 5, 1099–1103PubMedCrossRefGoogle Scholar
  150. 150.
    Meghji, S., Morrison, M. S., Henderson, B., and Arnett, T. R. (2001) pH dependence of bone resorption: mouse calvarial osteoclasts are activated by acidosis. Am. J. Physiol. Endocrinol. Metab. 280, E112–E119.PubMedGoogle Scholar
  151. 151.
    Tani-Ishii, N., Tsunoda, A., and Umemoto, T. (1997) Osteopontin antisense deoxyoligonucleotides inhibit bone resorption by mouse osteoclasts in vitro. J. Periodont. Res. 32, 480–486.PubMedCrossRefGoogle Scholar
  152. 152.
    Asou, Y., Rittling, S. R., Yoshitake, H., Tsuji, K., Shinomiya, K., Nifuji, A., et al. (2001) Osteopontin facilitates angiogenesis, accumulation of osteoclasts and resorption in ectopic bone. Endocrinology 142, 1325–1332.PubMedCrossRefGoogle Scholar
  153. 153.
    Kaneko, H., Arakawa, T., Mano, H., Kaneda, T., Ogasawara, A., Nakagawa, M., et al. (2000) Direct stimulation of osteoclastic bone resorption by bone morphogenetic protein (BMP-2) and expression of BMP receptors in mature osteoclasts. Bone 27, 479–486.PubMedCrossRefGoogle Scholar
  154. 154.
    Otsuka, E., Kato, Y., Hirose, S., and Hagiwara, H. (2000) Role of ascorbic acid in the osteoclast formation: induction of osteoclast differentiation factor with formation of the extracellular collagen matrix. Endocrinology 141, 3006–3011.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2004

Authors and Affiliations

  • Sakamuri V. Reddy
  • G. David Roodman

There are no affiliations available

Personalised recommendations