Abstract
The last several decades have revealed numerous interactions between cells of the hematopoietic lineage and osteoblasts (OBs) of the mesenchymal lineage. For example, OBs are important players in the hematopoietic stem cell (HSC) niche and OBs are known to impact osteoclast (OC) development. Thus, although much is known regarding the impact OBs have on hematopoietic cells, less is known about the impact of hematopoietic cells on OBs. Here we will review this reciprocal relationship: the effects of hematopoietic cells on OBs. Specifically, we will examine the impact of hematopoietic cells such as HSCs, lymphocytes, and megakaryocytes, as well as the hematopoietic cell–derived OCs on OB proliferation, differentiation, and function.
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Marie PJ. Transcription factors controlling osteoblastogenesis. Arch Biochem Biophys. 2008;473:98–105.
Giuliani N, Colla S, Morandi F, et al. Myeloma cells block RUNX2/CBFA1 activity in human bone marrow osteoblast progenitors and inhibit osteoblast formation and differentiation. Blood. 2005;106:2472–83.
Ehrlich LA, Chung HY, Ghobrial I, et al. IL-3 is a potential inhibitor of osteoblast differentiation in multiple myeloma. Blood. 2005;106:1407–14.
• Lymperi S, Ferraro F, Scadden DT. The HSC niche concept has turned 31. Has our knowledge matured? Ann N Y Acad Sci. 2010;1192:12–8. This review article discusses the role of OBs as well as other cells in supporting HSCs.
Schofield R. The relationship between the spleen colony-forming cell and the haemopoietic stem cell. Blood Cells. 1978;4:7–25.
Calvi LM, Adams GB, Weibrecht KW, et al. Osteoblastic cells regulate the haematopoietic stem cell niche. Nature. 2003;425:841–6.
Zhang J, Niu C, Ye L, et al. Identification of the haematopoietic stem cell niche and control of the niche size. Nature. 2003;425:836–41.
• Kiel MJ, Morrison SJ. Uncertainty in the niches that maintain haematopoietic stem cells. Nat Rev Immunol. 2008;8:290–301. This review nicely clarifies the confusing use of the word “osteoblast” when referring to cells on the surface of bone within the HSC niche. This review nicely clarifies the confusing use of the word “osteoblast” when referring to cells on the surface of bone within the HSC niche.
• Porter RL, Calvi LM. Communications between bone cells and hematopoietic stem cells. Arch Biochem Biophys. 2008;473:193–200. This review article discusses the role of OBs as well as other cells in supporting HSCs.
Purton LE, Scadden DT. The hematopoietic stem cell niche (November 15, 2008). In: Silberstein L, editors. StemBook. The Stem Cell Research Community, StemBook, 2008, doi:10.3824/stembook.1.28.1, http://www.stembook.org
Chitteti BR, Cheng YH, Streicher DA, et al. Osteoblast lineage cells expressing high levels of Runx2 enhance hematopoietic progenitor cell proliferation and function. J Cell Biochem. 2010;111:284–94.
Cheng YH, Chitteti BR, Streicher DA, et al. Impact of osteoblast maturational status on their ability to enhance the hematopoietic function of stem and progenitor cells. J Bone Miner Res. 2010 [Epub ahead of print].
Chitteti BR, Cheng YH, Poteat B, et al. Impact of interactions of cellular components of the bone marrow microenvironment on hematopoietic stem and progenitor cell function. Blood. 2010;115:3239–48.
Weber JM, Forsythe SR, Christianson CA, et al. Parathyroid hormone stimulates expression of the notch ligand Jagged1 in osteoblastic cells. Bone. 2006;39:485–93.
Silverman GJ, Carson DA. Roles of B cells in rheumatoid arthritis. Arthritis Res Ther. 2003;5 Suppl 4:S1–6.
Shu ST, Martin CK, Thudi NK, et al. Osteolytic bone resorption in adult T-cell leukemia/lymphoma. Leuk Lymphoma. 2010;51:702–14.
Silvestris F, Cafforio P, Tucci M, et al. Upregulation of osteoblast apoptosis by malignant plasma cells: a role in myeloma bone disease. Br J Haematol. 2003;122:39–52.
•• Hayer S, Polzer K, Brandl A, et al. B-cell infiltrates induce endosteal bone formation in inflammatory arthritis. J Bone Miner Res. 2008;23:1650–60. This article shows that reduced numbers of B cells in mice having inflammatory arthritis are associated with reduced OB number and bone formation.
Mohanty ST, Kottam L, Gambardella A, et al. Alterations in the self-renewal and differentiation ability of bone marrow mesenchymal stem cells in a mouse model of rheumatoid arthritis. Arthritis Res Ther. 2010;12:R149.
Udagawa N, Kotake S, Kamatani N, et al. The molecular mechanism of osteoclastogenesis in rheumatoid arthritis. Arthritis Res. 2002;4:281–9.
Edwards CM, Mundy GR. Eph receptors and ephrin signaling pathways: a role in bone homeostasis. Int J Med Sci. 2008;5:263–72.
Sanchez-Fernandez MA, Gallois A, Riedl T, et al. Osteoclasts control osteoblast chemotaxis via PDGF-BB/PDGF receptor beta signaling. PLoS ONE. 2008;3:e3537.
Luiz de Freitas PH, Li M, Ninomiya T, et al. Intermittent PTH administration stimulates pre-osteoblastic proliferation without leading to enhanced bone formation in osteoclast-less c-fos(−/−) mice. J Bone Miner Res. 2009;24:1586–97.
Zhao C, Irie N, Takada Y, et al. Bidirectional ephrinB2-EphB4 signaling controls bone homeostasis. Cell Metab. 2006;4:111–21.
Pennisi A, Ling W, Li X, et al. The ephrinB2/EphB4 axis is dysregulated in osteoprogenitors from myeloma patients and its activation affects myeloma bone disease and tumor growth. Blood. 2009;114:1803–12.
• Chang MK, Raggatt LJ, Alexander KA, et al. Osteal tissue macrophages are intercalated throughout human and mouse bone lining tissues and regulate osteoblast function in vitro and in vivo. J Immunol. 2008;181:1232–44. This article describes the ability of macrophages to modulate OB mineralization.
Kacena MA, Shivdasani RA, Wilson K, et al. Megakaryocyte-osteoblast interaction revealed in mice deficient in transcription factors GATA-1 and NF-E2. J Bone Miner Res. 2004;19:652–60.
Ciovacco WA, Goldberg CG, Taylor AF, et al. The role of gap junctions in megakaryocyte-mediated osteoblast proliferation and differentiation. Bone. 2009;44:80–6.
Lemieux JM, Horowitz MC, Kacena MA. Involvement of integrins alpha(3)beta(1) and alpha(5)beta(1) and glycoprotein IIb in megakaryocyte-induced osteoblast proliferation. J Cell Biochem. 2010;109:927–32.
Ciovacco WA, Cheng YH, Horowitz MC, Kacena MA. Immature and mature megakaryocytes enhance osteoblast proliferation and inhibit osteoclast formation. J Cell Biochem. 2010;109:774–81.
Frey BM, Rafii S, Teterson M, et al. Adenovector-mediated expression of human thrombopoietin cDNA in immune-compromised mice: Insights into the pathophysiology of osteomyelofibrosis. J Immunol. 1998;160:691–9.
Yan XQ, Lacey D, Hill D, et al. A model of myelofibrosis and osteosclerosis in mice induced by overexpressing thrombopoietin (mpl ligand): reversal of disease by bone marrow transplantation. Blood. 1996;88:402–9.
Villeval JL, Cohen-Solal K, Tulliez M, et al. High thrombopoietin production by hematopoietic cells induces a fatal myeloproliferative syndrome in mice. Blood. 1997;90:4369–83.
Suva LJ, Hartman E, Dilley JD, et al. Platelet dysfunction and a high bone mass phenotype in a murine model of platelet-type von willebrand disease. Am J Pathol. 2008;172:430–9.
Kacena MA, Nelson T, Clough ME, et al. Megakaryocyte-mediated inhibition of osteoclast development. Bone. 2006;39:991–9.
Beeton CA, Bord S, Ireland D, Compston JE. Osteoclast formation and bone resorption are inhibited by megakaryocytes. Bone. 2006;39:985–90.
• Dominici M, Rasini V, Bussolari R, et al. Restoration and reversible expansion of the osteoblastic hematopoietic stem cell niche after marrow radioablation. Blood. 2009;114:2333–43. This article shows that following lethal irradiation, MKs migrate to endosteal bone surfaces and stimulate OB proliferation.
Kacena MA, Gundberg CM, Nelson T, Horowitz MC. Loss of the transcription factor p45 NF-E2 results in a developmental arrest of megakaryocyte differentiation and the onset of a high bone mass phenotype. Bone. 2005;36:215–23.
Bord S, Vedi S, Beavan SR, et al. Megakaryocyte population in human bone marrow increases with estrogen treatment: a role in bone remodeling? Bone. 2000;27:397–401.
Bord S, Frith E, Ireland DC, et al. Synthesis of osteoprotegerin and RANKL by megakaryocytes is modulated by oestrogen. Br J Haematol. 2004;126:244–51.
Heiss CJ, Sanborn CF, Nichols DL, et al. Associations of body fat distribution, circulating sex hormones, and bone density in postmenopausal women. J Clin Endocrinol Metab. 1995;80:1591–6.
Thiele J, Kvasnicka HM, Fischer R. Histochemistry and morphometry on bone marrow biopsies in chronic myeloproliferative disorders—aids to diagnosis and classification. Ann Hematol. 1999;78:495–506.
Chagraoui H, Wendling F, Vainchenker W. Pathogenesis of myelofibrosis with myeloid metaplasia: Insight from mouse models. Best Pract Res Clin Haematol. 2006;19:399–412.
Miao D, Murant S, Scutt N, et al. Megakaryocyte-bone marrow stromal cell aggregates demonstrate increased colony formation and alkaline phosphatase expression in vitro. Tissue Eng. 2004;10:807–17.
Willecke K, Eiberger J, Degen J, et al. Structural and functional diversity of connexin genes in the mouse and human genome. Biol Chem. 2002;383:725–37.
Krenacs T, Rosendaal M. Connexin43 gap junctions in normal, regenerating, and cultured mouse bone marrow and in human leukemias: Their possible involvement in blood formation. Am J Pathol. 1998;152:993–1004.
Donahue HJ. Gap junctions and biophysical regulation of bone cell differentiation. Bone. 2000;26:417–22.
Schmitz B, Thiele J, Otto F, et al. Evidence for integrin receptor involvement in megakaryocyte-fibroblast interaction: a possible pathomechanism for the evolution of myelofibrosis. J Cell Physiol. 1998;176:445–55.
Wickenhauser C, Schmitz B, Baldus SE, et al. Selectins (CD62L, CD62P) and megakaryocytic glycoproteins (CD41a, CD42b) mediate megakaryocyte-fibroblast interactions in human bone marrow. Leuk Res. 2000;24:1013–21.
Bord S, Frith E, Ireland DC, et al. Megakaryocytes modulate osteoblast synthesis of type-l collagen, osteoprotegerin, and RANKL. Bone. 2005;36:812–9.
Acknowledgments
We would like to thank our long-time collaborator Dr. Mark C. Horowitz for his role on our published studies that we discussed here. This work was supported by the Indiana—Clinical and Translational Sciences Institute funded, in part by National Institutes of Health (NIH) grants NCRR RR025760 and RR025761 (MAK), the Department of Orthopaedic Surgery, Indiana University School of Medicine (MAK), and by NIH grant NIAMS R03 AR055269 (MAK).
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Conflicts of interest: M. Bethel: none; E.F. Srour: none; M. A. Kacena: none.
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Bethel, M., Srour, E.F. & Kacena, M.A. Hematopoietic Cell Regulation of Osteoblast Proliferation and Differentiation. Curr Osteoporos Rep 9, 96–102 (2011). https://doi.org/10.1007/s11914-011-0048-1
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DOI: https://doi.org/10.1007/s11914-011-0048-1