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. 1994 May 1;179(5):1677–1682. doi: 10.1084/jem.179.5.1677

Human osteoblasts support hematopoiesis through the production of granulocyte colony-stimulating factor

PMCID: PMC2191506  PMID: 7513014

Abstract

Previous attempts at identifying the constitutive source(s) of granulocyte colony-stimulating factor (G-CSF) in human bone marrow have been unsuccessful despite the fact that normal bone marrow supports abundant myelopoiesis in vivo. We hypothesized that the intimate physical association between bone and hematopoietic cells facilitates interactions between osteoblasts and hematopoietic stem cells. Here we provide the first direct evidence that human osteoblasts participate in hematopoiesis by constitutively producing G-CSF and present the protein in a membrane-associated fashion to human hematopoietic progenitors. These results suggest a direct and central role for osteoblasts in normal myelopoiesis.

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Selected References

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  1. Benayahu D., Fried A., Zipori D., Wientroub S. Subpopulations of marrow stromal cells share a variety of osteoblastic markers. Calcif Tissue Int. 1991 Sep;49(3):202–207. doi: 10.1007/BF02556119. [DOI] [PubMed] [Google Scholar]
  2. Benayahu D., Horowitz M., Zipori D., Wientroub S. Hemopoietic functions of marrow-derived osteogenic cells. Calcif Tissue Int. 1992 Sep;51(3):195–201. doi: 10.1007/BF00334547. [DOI] [PubMed] [Google Scholar]
  3. Dexter T. M., Coutinho L. H., Spooncer E., Heyworth C. M., Daniel C. P., Schiro R., Chang J., Allen T. D. Stromal cells in haemopoiesis. Ciba Found Symp. 1990;148:76–95. doi: 10.1002/9780470513880.ch6. [DOI] [PubMed] [Google Scholar]
  4. Dorheim M. A., Sullivan M., Dandapani V., Wu X., Hudson J., Segarini P. R., Rosen D. M., Aulthouse A. L., Gimble J. M. Osteoblastic gene expression during adipogenesis in hematopoietic supporting murine bone marrow stromal cells. J Cell Physiol. 1993 Feb;154(2):317–328. doi: 10.1002/jcp.1041540215. [DOI] [PubMed] [Google Scholar]
  5. Fava R. A., McClure D. B. Fibronectin-associated transforming growth factor. J Cell Physiol. 1987 May;131(2):184–189. doi: 10.1002/jcp.1041310207. [DOI] [PubMed] [Google Scholar]
  6. Felix R., Cecchini M. G., Hofstetter W., Guenther H. L., Fleisch H. Production of granulocyte-macrophage (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) by rat clonal osteoblastic cell population CRP 10/30 and the immortalized cell line IRC10/30-myc1 stimulated by tumor necrosis factor alpha. Endocrinology. 1991 Feb;128(2):661–667. doi: 10.1210/endo-128-2-661. [DOI] [PubMed] [Google Scholar]
  7. Felix R., Elford P. R., Stoercklé C., Cecchini M., Wetterwald A., Trechsel U., Fleisch H., Stadler B. M. Production of hemopoietic growth factors by bone tissue and bone cells in culture. J Bone Miner Res. 1988 Feb;3(1):27–36. doi: 10.1002/jbmr.5650030106. [DOI] [PubMed] [Google Scholar]
  8. Fibbe W. E., van Damme J., Billiau A., Goselink H. M., Voogt P. J., van Eeden G., Ralph P., Altrock B. W., Falkenburg J. H. Interleukin 1 induces human marrow stromal cells in long-term culture to produce granulocyte colony-stimulating factor and macrophage colony-stimulating factor. Blood. 1988 Feb;71(2):430–435. [PubMed] [Google Scholar]
  9. Gordon M. Y., Riley G. P., Watt S. M., Greaves M. F. Compartmentalization of a haematopoietic growth factor (GM-CSF) by glycosaminoglycans in the bone marrow microenvironment. 1987 Mar 26-Apr 1Nature. 326(6111):403–405. doi: 10.1038/326403a0. [DOI] [PubMed] [Google Scholar]
  10. Greenfield E. M., Gornik S. A., Horowitz M. C., Donahue H. J., Shaw S. M. Regulation of cytokine expression in osteoblasts by parathyroid hormone: rapid stimulation of interleukin-6 and leukemia inhibitory factor mRNA. J Bone Miner Res. 1993 Oct;8(10):1163–1171. doi: 10.1002/jbmr.5650081003. [DOI] [PubMed] [Google Scholar]
  11. Guba S. C., Sartor C. I., Gottschalk L. R., Jing Y. H., Mulligan T., Emerson S. G. Bone marrow stromal fibroblasts secrete interleukin-6 and granulocyte-macrophage colony-stimulating factor in the absence of inflammatory stimulation: demonstration by serum-free bioassay, enzyme-linked immunosorbent assay, and reverse transcriptase polymerase chain reaction. Blood. 1992 Sep 1;80(5):1190–1198. [PubMed] [Google Scholar]
  12. Hauschka P. V., Lian J. B., Cole D. E., Gundberg C. M. Osteocalcin and matrix Gla protein: vitamin K-dependent proteins in bone. Physiol Rev. 1989 Jul;69(3):990–1047. doi: 10.1152/physrev.1989.69.3.990. [DOI] [PubMed] [Google Scholar]
  13. Kittler E. L., McGrath H., Temeles D., Crittenden R. B., Kister V. K., Quesenberry P. J. Biologic significance of constitutive and subliminal growth factor production by bone marrow stroma. Blood. 1992 Jun 15;79(12):3168–3178. [PubMed] [Google Scholar]
  14. Kurt-Jones E. A., Beller D. I., Mizel S. B., Unanue E. R. Identification of a membrane-associated interleukin 1 in macrophages. Proc Natl Acad Sci U S A. 1985 Feb;82(4):1204–1208. doi: 10.1073/pnas.82.4.1204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Long M. W., Williams J. L., Mann K. G. Expression of human bone-related proteins in the hematopoietic microenvironment. J Clin Invest. 1990 Nov;86(5):1387–1395. doi: 10.1172/JCI114852. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lord B. I. The architecture of bone marrow cell populations. Int J Cell Cloning. 1990 Sep;8(5):317–331. doi: 10.1002/stem.5530080501. [DOI] [PubMed] [Google Scholar]
  17. Mayani H., Guilbert L. J., Janowska-Wieczorek A. Biology of the hemopoietic microenvironment. Eur J Haematol. 1992 Nov;49(5):225–233. doi: 10.1111/j.1600-0609.1992.tb00053.x. [DOI] [PubMed] [Google Scholar]
  18. Reddi A. H., Kuettner K. E. Vascular invasion of cartilage: correlation of morphology with lysozyme, glycosaminoglycans, protease, and protease-inhibitory activity during endochondral bone development. Dev Biol. 1981 Mar;82(2):217–223. doi: 10.1016/0012-1606(81)90447-4. [DOI] [PubMed] [Google Scholar]
  19. Roberts R., Gallagher J., Spooncer E., Allen T. D., Bloomfield F., Dexter T. M. Heparan sulphate bound growth factors: a mechanism for stromal cell mediated haemopoiesis. Nature. 1988 Mar 24;332(6162):376–378. doi: 10.1038/332376a0. [DOI] [PubMed] [Google Scholar]
  20. Robey P. G., Termine J. D. Human bone cells in vitro. Calcif Tissue Int. 1985 Sep;37(5):453–460. [PubMed] [Google Scholar]
  21. Shirafuji N., Asano S., Matsuda S., Watari K., Takaku F., Nagata S. A new bioassay for human granulocyte colony-stimulating factor (hG-CSF) using murine myeloblastic NFS-60 cells as targets and estimation of its levels in sera from normal healthy persons and patients with infectious and hematological disorders. Exp Hematol. 1989 Feb;17(2):116–119. [PubMed] [Google Scholar]
  22. Stein J., Borzillo G. V., Rettenmier C. W. Direct stimulation of cells expressing receptors for macrophage colony-stimulating factor (CSF-1) by a plasma membrane-bound precursor of human CSF-1. Blood. 1990 Oct 1;76(7):1308–1314. [PubMed] [Google Scholar]
  23. Taichman R. S., Hauschka P. V. Effects of interleukin-1 beta and tumor necrosis factor-alpha on osteoblastic expression of osteocalcin and mineralized extracellular matrix in vitro. Inflammation. 1992 Dec;16(6):587–601. doi: 10.1007/BF00919342. [DOI] [PubMed] [Google Scholar]
  24. Thies R. S., Bauduy M., Ashton B. A., Kurtzberg L., Wozney J. M., Rosen V. Recombinant human bone morphogenetic protein-2 induces osteoblastic differentiation in W-20-17 stromal cells. Endocrinology. 1992 Mar;130(3):1318–1324. doi: 10.1210/endo.130.3.1311236. [DOI] [PubMed] [Google Scholar]
  25. Toksoz D., Zsebo K. M., Smith K. A., Hu S., Brankow D., Suggs S. V., Martin F. H., Williams D. A. Support of human hematopoiesis in long-term bone marrow cultures by murine stromal cells selectively expressing the membrane-bound and secreted forms of the human homolog of the steel gene product, stem cell factor. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7350–7354. doi: 10.1073/pnas.89.16.7350. [DOI] [PMC free article] [PubMed] [Google Scholar]

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