Osteoclast Precursor Cells

  • Joseph A. Lorenzo
Part of the Advances in Experimental Medicine and Biology book series (volume 602)

The hematopoietic origin of the osteoclast is now clear. Walker (Walker 1975b, Walker 1975a, Walker 1975c) first demonstrated that the precursor cells of osteoclasts were hematopoietic. These studies showed that the transplant of spleen cells from osteopetrotic mice, which have dysfunctional osteoclasts, into irradiated normal animals caused the normal animals to become osteopetrotic within four weeks. Conversely, it was shown that transplant of normal spleen cells into irradiated osteopetrotic mice caused the osteopetrotic mice to develop normal bone remodeling within the same time period. More recently, bone marrow transplants into humans with osteopetrosis have, in selected cases, led to reversal of the condition (Coccia, Krivit, Cervenka, et al. 1980).

Testa et al. first illustrated that feline bone marrow cultures could be induced to form multinucleated osteoclast-like cells (OCL) (Testa, Allen, Lajtha, et al. 1981, Allen, Testa, Suda, et al. 1981). Subsequently, Ibbotson et al characterized this system and demonstrated that stimulators of bone resorption enhanced the rate of formation of OCL (Ibbotson, Roodman, McManus, et al. 1984). Culture systems that use human or mouse marrow have been extensively studied and these demonstrate that the OCL that form have many characteristics of true osteoclasts. These include the abundant production of tartrate resistant acid phosphatase (TRAP) and calcitonin receptors (CTR) as well as the ability to form resorption lacunae when the cells are cultured on dentin or bone slices. Udagawa et al showed that spleen cells from mice could be cultured with stromal cell lines or primary osteoblastic cells and induced to form OCL (Udagawa, Takahashi, Akatsu, et al. 1989). The cells formed numerous resorption lacunae and had other characteristics of true osteoclasts. These authors also demonstrated that cell contact between hematopoietic osteoclast precursors in the spleen cell population and stromal or osteoblastic precursors was essential for osteoclast formation.


Tartrate Resistant Acid Phosphatase Osteoclast Precursor Murine Bone Marrow Stromal Cell Line Osteoclast Precursor Cell 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Akashi, K., D. Traver, T. Miyamoto, and I.L. Weissman. 2000. A clonogenic common myeloid progenitor that gives rise to all myeloid lineages. Nature 404(6774): 193–197.CrossRefPubMedGoogle Scholar
  2. Allen, T.D., N.G. Testa, T. Suda, S.L Schor, D. Onions, et al. 1981. The production of putative osteoclasts in tissue culture - ultrastructure, formation and behavior. Scan Electron Microsc (Pt 3): 347–354.Google Scholar
  3. Alnaeeli, M., J.M. Penninger, and Y.T. Teng. 2006. Immune Interactions with CD4+ T Cells Promote the Development of Functional Osteoclasts from Murine CD11c+ Dendritic Cells. J Immunol 177(5): 3314–3326.PubMedGoogle Scholar
  4. Arai, F., T. Miyamoto, O. Ohneda, T. Inada, T. Sudo, et al. 1999. Commitment and differentiation of osteoclast precursor cells by the sequential expression of c-Fms and receptor activator of nuclear factor kappaB (RANK) receptors. J Exp Med 190(12): 1741–1754.CrossRefPubMedGoogle Scholar
  5. Athanasou N.A., A. Heryet, J. Quinn, K.C. Gatter, D.Y. Mason, and J.O. McGee. 1986. Osteoclasts contain macrophage and megakaryocyte antigens. J Pathol 150(4): 239–246.CrossRefPubMedGoogle Scholar
  6. Blin-Wakkach C., A. Wakkach, N. Rochet, and G.F. Carle. 2004. Characterization of a novel bipotent hematopoietic progenitor population in normal and osteopetrotic mice. J Bone Miner Res 19(7): 1137–1143.CrossRefPubMedGoogle Scholar
  7. Cecchini, M.G., W. Hofstetter, J. Halasy, A. Wetterwald, and R. Felix. 1997. Role of CSF-1 in bone and bone marrow development. Mol Reproduct Develop 46(1): 75–84.CrossRefGoogle Scholar
  8. Coccia P.F., W. Krivit, J. Cervenka, C. Clawson, J.H. Kersey, et al. 1980. Successful bone-marrow transplantation for infantile malignant osteopetrosis. N Engl J Med 302(13): 701–708.PubMedCrossRefGoogle Scholar
  9. Colonna, M. 2003. DAP12 signaling: from immune cells to bone modeling and brain myelination. J Clin Invest 111(3): 313–314.PubMedGoogle Scholar
  10. De, K.B., I. Carpentier, R.J. Lories, Y. Habraken, J. Piette, et al. 2004. Enhanced osteoclast development in collagen-induced arthritis in interferon-gamma receptor knock-out mice as related to increased splenic CD11b+ myelopoiesis. Arthritis Res Ther 6(3): R220–R231.CrossRefGoogle Scholar
  11. Fogg, D.K., C. Sibon, C. Miled, S. Jung, P. Aucouturier, et al. 2006. A clonogenic bone marrow progenitor specific for macrophages and dendritic cells. Science 311(5757): 83–87.CrossRefPubMedGoogle Scholar
  12. Fujikawa, Y., J.M.W. Quinn, A. Sabokbar, J.O. McGee, and N.A., Athanasou. 1996. The human osteoclast precursor circulates in the monocyte fraction. Endocrinology 137: 4058–4060.CrossRefPubMedGoogle Scholar
  13. Hayashi, S., A. Miyamoto, T. Yamane, H. Kataoka, M. Ogawa, et al. 1997. Osteoclast precursors in bone marrow and peritoneal cavity. J Cell Physiol 170(3): 241–247.CrossRefPubMedGoogle Scholar
  14. Horowitz, M.C., Y. Xi, D.L. Pflugh, D.G. Hesslein, D.G. Schatz, et al. 2004. Pax5-deficient mice exhibit early onset osteopenia with increased osteoclast progenitors. J Immunol 173(11): 6583–6591.PubMedGoogle Scholar
  15. Ibbotson, K.J., G.D. Roodman, L.M. McManus, and G.R. Mundy. 1984. Identification and characterization of osteoclast-like cells and their progenitors in cultures of feline marrow mononuclear cells. J Cell Biol 99(2): 471–480.CrossRefPubMedGoogle Scholar
  16. Jacquin, C., D.E. Gran, S.K. Lee, J.A. Lorenzo, and H.L. Aguila. 2006. Identification of multiple osteoclast precursor populations in murine bone marrow. J Bone Miner Res 21(1): 67–77.CrossRefPubMedGoogle Scholar
  17. Katavic, V., D. Grcevic, S.K. Lee, J. Kalinowski, S. Jastrzebski, et al. 2003. The surface antigen CD45R identifies a population of estrogen-regulated murine marrow cells that contain osteoclast precursors. Bone 32(6): 581–590.CrossRefPubMedGoogle Scholar
  18. Koga, T., M. Inui, K. Inoue, S. Kim, A. Suematsu, et al. 2004. Costimulatory signals mediated by the ITAM motif cooperate with RANKL for bone homeostasis. Nature 428(6984): 758–763.CrossRefPubMedGoogle Scholar
  19. Kondo, M., I.L. Weissman, and K. Akashi. 1997. Identification of clonogenic common lymphoid progenitors in mouse bone marrow. Cell 91(5):661–672.CrossRefPubMedGoogle Scholar
  20. Kukita, T., and G.D. Roodman. 1989. Development of a monoclonal antibody to osteoclasts formed in vitro which recognizes mononuclear osteoclast precursors in the marrow. Endocrinology 125(2): 630–637.CrossRefPubMedGoogle Scholar
  21. Li, P., E.M. Schwarz, R.J. O’Keefe, L. Ma, B.F. Boyce, and L. Xing. 2004a. RANK signaling is not required for TNF alpha-mediated increase in CD11(hi) osteoclast precursors but is essential for mature osteoclast formation in TNF alpha-mediated inflammatory arthritis. J Bone Miner Res 19(2): 207–213.CrossRefPubMedGoogle Scholar
  22. Li P., E.M. Schwarz, R.J. O’Keefe, L. Ma, R.J. Looney, et al. 2004b. Systemic tumor necrosis factor alpha mediates an increase in peripheral CD11bhigh osteoclast precursors in tumor necrosis factor alpha-transgenic mice. Arthritis Rheum 50(1): 265–276.CrossRefPubMedGoogle Scholar
  23. Manabe, N., H. Kawaguchi, H. Chikuda, C. Miyaura, M. Inada, et al. 2001. Connection between B lymphocyte and osteoclast differentiation pathways. J Immunol 167(5): 2625–2631.PubMedGoogle Scholar
  24. Miyamoto, T., F. Arai, O. Ohneda, K. Takagi, D.M. Anderson, and T. Suda. 2000. An adherent condition is required for formation of multinuclear osteoclasts in the presence of macrophage colony-stimulating factor and receptor activator of nuclear factor kappaB ligand. Blood 96(13): 4335–4343.PubMedGoogle Scholar
  25. Miyamoto, T., O. Ohneda, F. Arai, K. Iwamoto, S. Okada, et al. 2001. Bifurcation of osteoclasts and dendritic cells from common progenitors. Blood 98(8): 2544–2554.CrossRefPubMedGoogle Scholar
  26. Muguruma, Y., and M.Y. Lee. 1998. Isolation and characterization of murine clonogenic osteoclast progenitors by cell surface phenotype analysis. Blood 91(4): 1272–1279.PubMedGoogle Scholar
  27. Picker, L.J., and M.H. Siegelman. 1999. Lymphoid tissues and organs. In Fundamental Immunology, ed. WE Paul, 14:479–531. Philadelphia: Lippincott-Raven.Google Scholar
  28. Quinn, J.M.W., A. Sabokbar, and N.A Athanasou. 1996. Cells of the mononuclear phagocyte series differentiate into osteoclastic lacunar bone resorbing cells. J Pathol 179:106–111.CrossRefPubMedGoogle Scholar
  29. Reis e Sousa. 2006. Dendritic cells in a mature age. Nat Rev Immunol 6(6): 476–483.CrossRefGoogle Scholar
  30. Rivollier, A., M. Mazzorana, J. Tebib, M. Piperno, T. Aitsiselmi, et al. 2004. Immature dendritic cell transdifferentiation into osteoclasts: a novel pathway sustained by the rheumatoid arthritis microenvironment. Blood 104(13): 4029–4037.CrossRefPubMedGoogle Scholar
  31. Sato, T., T. Shibata, K. Ikeda, and K. Watanabe. 2001. Generation of bone-resorbing osteoclasts from B220+ cells: its role in accelerated osteoclastogenesis due to estrogen deficiency. J Bone Miner Res 16(12): 2215–2221.CrossRefPubMedGoogle Scholar
  32. Servet-Delprat, C., S. Arnaud, P. Jurdic, S. Nataf, M.F. Grasset, et al. 2002. Flt3+ macrophage precursors commit sequentially to osteoclasts, dendritic cells and microglia. BMC Immunol 3: 15.CrossRefPubMedGoogle Scholar
  33. Sminia T., and C.D. Dijkstra. 1986. The origin of osteoclasts: an immunohistochemical study on macrophages and osteoclasts in embryonic rat bone. Calcif Tissue Int 39(4): 263–266.CrossRefPubMedGoogle Scholar
  34. Spangrude, G.J., S. Heimfeld, and I.L. Weissman. 1988. Purification and characterization of mouse hematopoietic stem cells [published erratum appears in Science 1989 Jun 2;244(4908):1030]. Science 241(4861): 58–62.CrossRefPubMedGoogle Scholar
  35. Testa, N.G., T.D. Allen, L.G. Lajtha, D. Onions, and O. Jarret. 1981. Generation of osteoclasts in vitro. J. Cell Sci 47: 127–137.PubMedGoogle Scholar
  36. Tsurukai, T., N. Takahashi, E. Jimi, I. Nakamura, N. Udagawa. et al. 1998. Isolation and characterization of osteoclast precursors that differentiate into osteoclasts on calvarial cells within a short period of time. J Cell Physiol 177(1): 26–35.CrossRefPubMedGoogle Scholar
  37. Uchida, N., and I.L. Weissman. 1992. Searching for hematopoietic stem cells: evidence that Thy-1.1lo Lin- Sca-1+ cells are the only stem cells in C57BL/Ka-Thy-1.1 bone marrow. J Exp Med 175(1): 175–184.CrossRefPubMedGoogle Scholar
  38. Udagawa, N., N. Takahashi, T. Akatsu, T. Sasaki, A. Yamaguchi, et al. 1989. The bone marrow-derived stromal cell lines MC3T3–G2/PA6 and ST2 support osteoclast-like cell differentiation in cocultures with mouse spleen cells. Endocrinology 125(4): 1805–1813.CrossRefPubMedGoogle Scholar
  39. Walker, D.G. 1975a. Bone resorption restored in osteopetrotic mice by transplants of normal bone marrow and spleen cells. Science 190(4216): 784–785.CrossRefPubMedGoogle Scholar
  40. Walker, D.G. 1975b. Control of bone resorption by hematopoietic tissue. J Exp Med 142: 651–663.CrossRefPubMedGoogle Scholar
  41. Walker, D.G. 1975c. Spleen cells transmit osteopetrosis in mice. Science 190(4216): 785–787.CrossRefPubMedGoogle Scholar
  42. Yao Z., P. Li, Q. Zhang, E.M. Schwarz, P. Keng, et al. 2006. Tnf increases circulating osteoclast precursor numbers by promoting their proliferation and differentiation in the bone marrow through up-regulation of c-fms expression. J Biol Chem.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Joseph A. Lorenzo
    • 1
  1. 1.Department of MedicineUniversity of Connecticut Health CenterNew HavenUSA

Personalised recommendations