Endocrinology, Vol 128, 259-262, Copyright © 1991 by Endocrine Society

ARTICLES

Identification of osteoclast precursors in multilineage hemopoietic colonies

G Hattersley, JA Kerby and TJ Chambers
Department of Histopathology, St. George's Hospital Medical School, London, United Kingdom.

The osteoclast is known to be derived from the hemopoietic stem cell, but its lineage and the mechanisms by which its differentiation is regulated are largely unknown. There is evidence that osteoclastic differentiation is induced through a contact-dependent interaction between bone marrow stromal cells and hemopoietic precursors. To analyze osteoclastic lineage, colonies were generated in semi-solid medium from mouse spleen cells in the presence of erythropoietin with either Wehi 3B-conditioned medium or interleukin 3 (IL3). After 7 days, individual colonies were picked. Half of each colony was phenotyped by the morphology of cells in cytospin preparations; the second half of each was incubated for 7 days with a bone marrow-derived cell line (ts8) that induces osteoclastic differentiation from hemopoietic cells, on bone slices in the presence of 1,25-dihydroxyvitamin D3. After incubation, bone resorption was assessed by scanning electron microscopy. No resorption was induced in cells derived from single- lineage colonies, but resorptive cells differentiated in 17% of granulocyte-macrophage (GM) colonies and 38% of multilineage colonies. Since only a minority of GM colonies contained osteoclastic precursors, this suggests that the GM colonies that contained osteoclasts were not typical GM colonies but may have been a form of multilineage colony analagous to other multilineage colonies that contain granulocytes, macrophages, and a third cell type. No resorptive cells were formed when IL3-derived colonies were incubated on bone slices without ts8 cells. The results suggest that osteoclasts are derived from a multilineage precursor, upon which IL3 acts to generate cells capable of osteoclastic differentiation, which form resorptive cells upon incubation with bone marrow stromal cells in the presence of 1,25- dihydroxyvitamin D3.

This article has been cited by other articles:

				K. Takada, M. Inaba, N. Ichioka, Y. Ueda, M. Taira, S. Baba, T. Mizokami, X. Wang, H. Hisha, H. Iida, et al. Treatment of Senile Osteoporosis in SAMP6 Mice by Intra-Bone Marrow Injection of Allogeneic Bone Marrow Cells Stem Cells, February 1, 2006; 24(2): 399 - 405. [Abstract] [Full Text] [PDF]

				J. M. Lean, K. Fuller, and T. J. Chambers FLT3 ligand can substitute for macrophage colony-stimulating factor in support of osteoclast differentiation and function Blood, November 1, 2001; 98(9): 2707 - 2713. [Abstract] [Full Text] [PDF]

				N. Manabe, H. Kawaguchi, H. Chikuda, C. Miyaura, M. Inada, R. Nagai, Y.-i. Nabeshima, K. Nakamura, A. M. Sinclair, R. H. Scheuermann, et al. Connection Between B Lymphocyte and Osteoclast Differentiation Pathways J. Immunol., September 1, 2001; 167(5): 2625 - 2631. [Abstract] [Full Text] [PDF]

				T. Suda, N. Takahashi, N. Udagawa, E. Jimi, M. T. Gillespie, and T. J. Martin Modulation of Osteoclast Differentiation and Function by the New Members of the Tumor Necrosis Factor Receptor and Ligand Families Endocr. Rev., June 1, 1999; 20(3): 345 - 357. [Abstract] [Full Text]

				Y. Muguruma and M. Y. Lee Isolation and Characterization of Murine Clonogenic Osteoclast Progenitors by Cell Surface Phenotype Analysis Blood, February 15, 1998; 91(4): 1272 - 1279. [Abstract] [Full Text] [PDF]

				T. Yamane, T. Kunisada, H. Yamazaki, T. Era, T. Nakano, and S.-I. Hayashi Development of Osteoclasts From Embryonic Stem Cells Through a Pathway That Is c-fms but not c-kit Dependent Blood, November 1, 1997; 90(9): 3516 - 3523. [Abstract] [Full Text] [PDF]

				R. S. Weinstein, R. L. Jilka, A. M. Parfitt, and S. C. Manolagas The Effects of Androgen Deficiency on Murine Bone Remodeling and Bone Mineral Density Are Mediated via Cells of the Osteoblastic Lineage Endocrinology, September 1, 1997; 138(9): 4013 - 4021. [Abstract] [Full Text] [PDF]

				F Solari, F Flamant, Y Cherel, M Wyers, and P Jurdic The osteoclast generation: an in vitro and in vivo study with a genetically labelled avian monocytic cell line J. Cell Sci., January 6, 1996; 109(6): 1203 - 1213. [Abstract] [PDF]

				S. C. Manolagas and R. L. Jilka Bone Marrow, Cytokines, and Bone Remodeling -- Emerging Insights into the Pathophysiology of Osteoporosis N. Engl. J. Med., February 2, 1995; 332(5): 305 - 311. [Full Text] [PDF]

				R. Jilka, G Hangoc, G Girasole, G Passeri, D. Williams, J. Abrams, B Boyce, H Broxmeyer, and S. Manolagas Increased osteoclast development after estrogen loss: mediation by interleukin-6 Science, July 3, 1992; 257(5066): 88 - 91. [Abstract] [PDF]