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Hemopoietic functions of marrow-derived osteogenic cells

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Summary

Osteoblasts, members of the marrow stromal cellular network, may play an active role in the hemopoietic microenvironment as well as in bone remodeling. In this study, we examined the extent to which marrow-derived osteogenic cells (MBA-15) possess various stromal functions. This marrow stromal-derived cell line was shown by us to exhibit osteoblastic characteristics in culture and to form bone in vivo. These cells are shown here to constitutively produce and secrete cytokines identified as M-CSF, GM-CSF, and IL-6. MBA-15 cells modulate growth of normal and malignant myeloid and lymphoid cells as well as leukemia cell lines in vitro. Cell-cell interactions were studied in co-cultures with adherent MBA-15 cells and the target hemopoietic cells. Growth inhibition effects, observed under various experimental conditions, can be attributed to the presence of different soluble and membrane-bound inhibitory activities produced by MBA-15 cells. Thus, MBA-15 cells spontaneously produce both stimulators and inhibitors that can affect myeloid and lymphoid cell growth. Marrow osteogenic cells may therefore participate in the stromal regulation of hemopoiesis.

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References

  1. Allen TD, Dexter TM (1983) Long-term bone marrow cultures: an ultrastructural review. Scan Electron Microscop 4:1851–1866

    Google Scholar 

  2. Lambertsen RH, Weiss L (1984) A model of intramedullary haemopoietic microenvironments based on sterologic study of the distribution of endoclonal marrow colonies. Blood 63:287–297

    Google Scholar 

  3. Marshall A, Lichtman MD (1981) The ultrastructure of the hemopoietic environment of the marrow: a review. Exp Hematol 9:391–410

    Google Scholar 

  4. Owen ME, Friedenstein AJ (1988) Stromal stem cells: marrowderived osteogenic precursors. In: Chichester (ed) Cell and molecular biology of vertebrate hard tissues. Ciba Foundation Symposium, 136 Wiley, pp 42–60

  5. Owen ME (1985) Lineage of osteogenic cells and their relationship to the stromal system. In: Peck WA (ed) Bone and mineral research, vol 3. Elsevier, Amsterdam, New York, Oxford, pp 1–25

    Google Scholar 

  6. Metcalf D (1989) The molecular control of cell division, differentiation, commitment and maturation in haemopoietic cells. Nature 339:27–30

    Google Scholar 

  7. Zipori D (1989) Stromal cells from the bone marrow. Evidence for a restrictive role in regulation of hemopoiesis. Eur J Haematol 42:225–232

    Google Scholar 

  8. Dexter TM, Testa NG, Allen TD, Rutherford T, Scolnick E (1981) Molecular and cell biology aspects of erythropoiesis in long-term bone marrow cultures. Blood 58:699–707

    Google Scholar 

  9. Zipori D, Friedman A, Tamir M, Silverberg D, Malik Z (1984) Cultured mouse marrow cell lines: interactions between fibroblastoid cells and monocytes. J Cell Physiol 118:143–152

    Google Scholar 

  10. Zipori D, Duksin D, Tamir M, Argaman A, Toledo J, Malik Z (1985) Cultured mouse marrow stromal cell lines II: distinct subtypes differing in morphology, collagen types, myelopoietic factors and leukemic cell growth modulation activities. J Cell Physiol 122:81–90

    Google Scholar 

  11. Benayahu D, Kletter J, Zipori D, Wientroub S (1989) Bone marrow-derived stromal cell line expressing osteoblastic phenotype in vitro and osteogenic capacity in vivo. J Cell Physiol 140:1–7

    Google Scholar 

  12. Benayahu D, Fried A, Zipori D, Wientroub S (1991) Subpopulations of marrow stromal cells share a variety of osteoblastic markers. Calcif Tissue Int 49:202–207

    Google Scholar 

  13. Zipori D (1990) Regulation of hemopoiesis by cytokines that restrict options for growth and differentiation. Cancer Cells 2(7):205–211

    Google Scholar 

  14. Morgan C, Pollard JW, Stanley ER (1987) Isolation and characterization of a cloned growth factor-dependent macrophage cell line BAC1.2F5. J Cell Physiol 130:420–427

    Google Scholar 

  15. Greenberger JS, Sakakeeny MA, Humphries RK, Eaves CJ, Eckner RJ (1983) Demonstration of permanent factor-dependent multipotential (erythroid/neutrophil/basophil) hemotopoietic progenitor cell lines. Proc Natl Acad Sci 80:2931–2935

    Google Scholar 

  16. Conlon PJ (1983) A rapid biological assay for the detection of interleukin 1. J Immunol 131(3):1280–1282

    Google Scholar 

  17. Watson J (1979) Continuous proliferation of murine antigen specific helper T lymphocytes in culture. J Exp Med 150:1510–1519

    Google Scholar 

  18. Nabel G, Galli SJ, Dvorak AM, Dvorak HF, Cantor H (1981) Inducer T lymphocytes synthesize a factor that stimulates proliferation of cloned mast cells. Nature 291:332–334

    Google Scholar 

  19. Aarden LA, DeGroot ER, Schaap OL, Lansdorp PM (1987) Production of hybridoma growth factor by human monocytes. Eur J Immunol 17:1411–1416

    Google Scholar 

  20. Zipori D, Tamir M, Toledo J, Oren T (1986) Differentiation stage and lineage-specific inhibitor from stroma of mouse bone marrow that restricts lymphoma cell growth. Proc Natl Sci 83: 4547–4551

    Google Scholar 

  21. Feyen JHM, Elford P, Di Padova FE, Trechsel U (1989) Interleukin-6 is produced by bone and modulated by parathyroid hormone. J Bone Miner Res 4(4):633–638

    Google Scholar 

  22. Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Method 65:55–63

    Google Scholar 

  23. Horowitz MC, Einhorn TA, Philbrick W, Jilka RL (1989a) Functional and molecular changes in colony-stimulating factor secretion by osteoblasts. Connect Tissue Res 20:159–168

    Google Scholar 

  24. Felix R, Elford PR, Stoerckle C, Cecchini M, Wetterwald A, Trechsel U, Fleisch H, Stadler BM (1988) Production of hemopoietic growth factors by bone tissue and bone cells in culture. J Bone Miner Res 3(1):27–36

    Google Scholar 

  25. Weir EC, Insogna KL, Horowitz MC (1989) Osteoblast-like cells secrete granulocyte-macrophage colony-stimulating factor in response to parathyroid hormone and lipopolysaccharide. Endocrinology 124(2):899–904

    Google Scholar 

  26. Horowitz MC, Coleman DL, Flood PM, Kupper TS, Jilka RL (1989) Parathyroid hormone and lipopolysaccharide induce murine osteoblast-like cells to secrete a cytokine indistinguishable from granulocyte-macrophage colony-stimulating factor. J Clin Invest 83:149–157

    Google Scholar 

  27. Elford PR, Felix R, Cecchini M, Trechsel U, Fleisch H (1987) Murine osteoblast-like cells and the osteogenic cell MC3T3-E1 release a macrophage colony-stimulating activity in culture. Calcif Tissue Int 41:151–156

    Google Scholar 

  28. Felix R, Fleisch H, Elford PR (1989) Bone-resorbing cytokines enhance release of macrophage colony-stimulating activity by the osteoblastic cell MC3T3-E1. Calcif Tissue Int 44:356–360

    Google Scholar 

  29. Horowitz MC, Coleman DL, Ryaby JT, Einhorn T (1989b) Osteotropic agents induce the differential secretion of granulocyte-macrophage colony-stimulating factor y the osteoblast cell line MC3T3-E1. J Bone Miner Res 4(6):911–919

    Google Scholar 

  30. Lotz M, Jirik F, Kabouridis P, Tsoukas C, Hirano T, Kishimoto T, Carson DA (1988) B cell-stimulating factor 2/interleukine 6 is a costimulant for human thymocytes and T lymphocytes. J Exp Med 167:1253–1258

    Google Scholar 

  31. Uyttenhove C, Coulie PG, Van Snick J (1988) T cell growth and differentiation induced by interleukin-HP1/IL-6, the murine hybridoma/plasmacytoma growth factor. J Exp Med 167:1417–1427

    Google Scholar 

  32. Ikebuchi K, Wong GG, Clark SC, Ihle JN, Hirai Y, Ogawa M (1987) Interleukin-6 enhancement of interleukin-3-dependent proliferation of multipotential hemopoietic progenitors. Proc Natl Acad Sci USA, 84;9035

    Google Scholar 

  33. Koike K, Nakahata T, Takagi M, Kobayashi T, Ishiguro A, Tsuji K, Naganuma K, Okano A, Akiyama Y, Akabane T (1988) Synergism of BSF-2/interleukin 6 and interleukin 3 on development of multipotential hemopoietic progenitors in serum-free culture. J Exp Med 168:879–890

    Google Scholar 

  34. Ishimi Y, Miyaura C, He Jim C, Akatsu T, Abe E, Nakamura Y, Yamaguchi A, Yoshiki S, Matsuda T, Hirano T, Kishimoto T, Suda T (1990) IL-6 produced by osteoblasts and induces bone resorption. J Immunol 145(10):3297–3303

    Google Scholar 

  35. Kurland J, Moore MAS (1977) Modulation of hemopoiesis by prostaglandins. Exp Hematol 5:357–373

    Google Scholar 

  36. Kurland JI, Bockman RS, Broxmeyer HE, Moore MAS (1978) Limitation of excessive myelopoiesis by the intrinsic modulation of macrophage-derived prostaglandin E. Science 199:552–555

    Google Scholar 

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Authors and Affiliations

  1. Department of Histology and Cell Biology, Sackler Eaculty of Medicine, Tel-Aviv University, 69978, Ramat-Aviv, Israel

    D. Benayahu & S. Wientroub

  2. Department of Orthopaedics, School of Medicine, Yale University, New Haven, Connecticut, USA

    M. Horowitz

  3. Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel

    D. Zipori

  4. Department of Pediatric Orthopaedics, Tel-Aviv Medical Center, Tel-Aviv, Israel

    S. Wientroub

Authors
  1. D. Benayahu
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  2. M. Horowitz
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  3. D. Zipori
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  4. S. Wientroub
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Benayahu, D., Horowitz, M., Zipori, D. et al. Hemopoietic functions of marrow-derived osteogenic cells. Calcif Tissue Int 51, 195–201 (1992). https://doi.org/10.1007/BF00334547

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  • DOI: https://doi.org/10.1007/BF00334547

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