Top

Published in:

01-03-2014 | Osteoimmunology (D Novack and G Schett, Section Editors)

Mesenchymal Progenitors and the Osteoblast Lineage in Bone Marrow Hematopoietic Niches

Authors: Cristina Panaroni, Yi-shiuan Tzeng, Hamid Saeed, Joy Y. Wu

Published in: Current Osteoporosis Reports | Issue 1/2014

Abstract

The bone marrow cavity is essential for the proper development of the hematopoietic system. In the last few decades, it has become clear that mesenchymal stem/progenitor cells as well as cells of the osteoblast lineage, besides maintaining bone homeostasis, are also fundamental regulators of bone marrow hematopoiesis. Several studies have demonstrated the direct involvement of mesenchymal and osteoblast lineage cells in the maintenance and regulation of supportive microenvironments necessary for quiescence, self-renewal and differentiation of hematopoietic stem cells. In addition, specific niches have also been identified within the bone marrow for maturing hematopoietic cells. Here we will review recent findings that have highlighted the roles of mesenchymal progenitors and cells of the osteoblast lineage in regulating distinct stages of hematopoiesis.

Weissman IL, Shizuru JA. The origins of the identification and isolation of hematopoietic stem cells, and their capability to induce donor-specific transplantation tolerance and treat autoimmune diseases. Blood. 2008;112(9):3543–53.PubMedCrossRef

Orkin SH, Zon LI. Hematopoiesis: an evolving paradigm for stem cell biology. Cell. 2008;132(4):631–44.PubMedCentralPubMedCrossRef

Ducy P, Zhang R, Geoffroy V, Ridall AL, Karsenty G. Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell. 1997;89(5):747–54.PubMedCrossRef

Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K, Deguchi K, et al. Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell. 1997;89(5):755–64.PubMedCrossRef

Nakashima K, Zhou X, Kunkel G, Zhang Z, Deng JM, Behringer RR, et al. The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell. 2002;108(1):17–29.PubMedCrossRef

Otto F, Thornell AP, Crompton T, Denzel A, Gilmour KC, Rosewell IR, et al. Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development. Cell. 1997;89(5):765–71.PubMedCrossRef

Aubin JE. Regulation of osteoblast formation and function. Rev Endocr Metab Disord. 2001;2(1):81–94.PubMedCrossRef

Manolagas SC. Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr Rev. 2000;21(2):115–37.PubMed

Matsuo K, Irie N. Osteoclast-osteoblast communication. Arch Biochem Biophys. 2008;473(2):201–9.PubMedCrossRef

10.

Taichman RS, Emerson SG. Human osteoblasts support hematopoiesis through the production of granulocyte colony-stimulating factor. J Exp Med. 1994;179(5):1677–82.PubMedCrossRef

11.

Taichman RS, Emerson SG. Human osteosarcoma cell lines MG-63 and SaOS-2 produce G-CSF and GM-CSF: identification and partial characterization of cell-associated isoforms. Exp Hematol. 1996;24(4):509–17.PubMed

12.

Taichman RS, Reilly MJ, Verma RS, Emerson SG. Augmented production of interleukin-6 by normal human osteoblasts in response to CD34+ hematopoietic bone marrow cells in vitro. Blood. 1997;89(4):1165–72.PubMed

13.

Malaval L, Aubin JE. Biphasic effects of leukemia inhibitory factor on osteoblastic differentiation. J Cell Biochem Suppl. 2001;Suppl 36:63–70.

14.

Nelissen JM, Torensma R, Pluyter M, Adema GJ, Raymakers RA, van Kooyk Y, et al. Molecular analysis of the hematopoiesis supporting osteoblastic cell line U2-OS. Exp Hematol. 2000;28(4):422–32.PubMedCrossRef

15.

Calvi LM, Adams GB, Weibrecht KW, Weber JM, Olson DP, Knight MC, et al. Osteoblastic cells regulate the haematopoietic stem cell niche. Nature. 2003;425(6960):841–6.PubMedCrossRef

16.

Zhang J, Niu C, Ye L, Huang H, He X, Tong WG, et al. Identification of the haematopoietic stem cell niche and control of the niche size. Nature. 2003;425(6960):836–41.PubMedCrossRef

17.

Visnjic D, Kalajzic I, Gronowicz G, Aguila HL, Clark SH, Lichtler AC, et al. Conditional ablation of the osteoblast lineage in Col2.3deltatk transgenic mice. J Bone Miner Res. 2001;16(12):2222–31.PubMedCrossRef

18.

Visnjic D, Kalajzic Z, Rowe DW, Katavic V, Lorenzo J, Aguila HL. Hematopoiesis is severely altered in mice with an induced osteoblast deficiency. Blood. 2004;103(9):3258–64.PubMedCrossRef

19.

Corral DA, Amling M, Priemel M, Loyer E, Fuchs S, Ducy P, et al. Dissociation between bone resorption and bone formation in osteopenic transgenic mice. Proc Natl Acad Sci U S A. 1998;95(23):13835–40.PubMedCentralPubMedCrossRef

20.

Shi S, Gronthos S. Perivascular niche of postnatal mesenchymal stem cells in human bone marrow and dental pulp. J Bone Miner Res. 2003;18(4):696–704.PubMedCrossRef

21.

Sacchetti B, Funari A, Michienzi S, Di Cesare S, Piersanti S, Saggio I, et al. Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment. Cell. 2007;131(2):324–36.PubMedCrossRef

22.

Tormin A, Li O, Brune JC, Walsh S, Schutz B, Ehinger M, et al. CD146 expression on primary nonhematopoietic bone marrow stem cells is correlated with in situ localization. Blood. 2011;117(19):5067–77.PubMedCrossRef

23.

Morikawa S, Mabuchi Y, Kubota Y, Nagai Y, Niibe K, Hiratsu E, et al. Prospective identification, isolation, and systemic transplantation of multipotent mesenchymal stem cells in murine bone marrow. J Exp Med. 2009;206(11):2483–96.PubMedCentralPubMedCrossRef

24.

Arai F, Yoshihara H, Hosokawa K, Nakamura Y, Gomei Y, Iwasaki H, et al. Niche regulation of hematopoietic stem cells in the endosteum. Ann N Y Acad Sci. 2009;1176:36–46.PubMedCrossRef

25.

Crisan M, Yap S, Casteilla L, Chen CW, Corselli M, Park TS, et al. A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell. 2008;3(3):301–13.PubMedCrossRef

26.

Corselli M, Chin CJ, Parekh C, Sahaghian A, Wang W, Ge S, et al. Perivascular support of human hematopoietic stem/progenitor cells. Blood. 2013;121(15):2891–901.PubMedCrossRef

27.

Stopp S, Bornhauser M, Ugarte F, Wobus M, Kuhn M, Brenner S, et al. Expression of the melanoma cell adhesion molecule in human mesenchymal stromal cells regulates proliferation, differentiation, and maintenance of hematopoietic stem and progenitor cells. Haematologica. 2013;98(4):505–13.PubMedCrossRef

28.

Isern J, Martin-Antonio B, Ghazanfari R, Martin AM, Lopez JA, del Toro R, et al. Self-renewing human bone marrow mesenspheres promote hematopoietic stem cell expansion. Cell Rep. 2013;3(5):1714–24.PubMedCrossRef

29.••

Mendez-Ferrer S, Michurina TV, Ferraro F, Mazloom AR, Macarthur BD, Lira SA, et al. Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature. 2010;466(7308):829–34. This paper demonstrated that perivascular mesenchymal stem cells support HSCs in vivo.PubMedCentralPubMedCrossRef

30.••

Ding L, Morrison SJ. Haematopoietic stem cells and early lymphoid progenitors occupy distinct bone marrow niches. Nature. 2013;495(7440):231–5. This article (along with Greenbaum, 2013) demonstrated that CXCL12 produced by mesenchymal stem/progenitor cells is required for HSC maintenance and retention, while CXCL12 produced by osteoprogenitors and osteoblasts supports B lymphopoiesis.PubMedCentralPubMedCrossRef

31.•

Ding L, Saunders TL, Enikolopov G, Morrison SJ. Endothelial and perivascular cells maintain haematopoietic stem cells. Nature. 2012;481(7382):457–62. This paper reported that deletion of SCF from mesenchymal progenitors but not maturing osteoblasts leads to loss of bone marrow HSPCs.PubMedCentralPubMedCrossRef

32.

Chan CK, Chen CC, Luppen CA, Kim JB, DeBoer AT, Wei K, et al. Endochondral ossification is required for haematopoietic stem-cell niche formation. Nature. 2009;457(7228):490–4.PubMedCentralPubMedCrossRef

33.

Chan CK, Lindau P, Jiang W, Chen JY, Zhang LF, Chen CC, et al. Clonal precursor of bone, cartilage, and hematopoietic niche stromal cells. Proc Natl Acad Sci U S A. 2013;110(31):12643–8.PubMedCentralPubMedCrossRef

34.

Broudy VC. Stem cell factor and hematopoiesis. Blood. 1997;90(4):1345–64.PubMed

35.

Tzeng YS, Li H, Kang YL, Chen WC, Cheng WC, Lai DM. Loss of Cxcl12/Sdf-1 in adult mice decreases the quiescent state of hematopoietic stem/progenitor cells and alters the pattern of hematopoietic regeneration after myelosuppression. Blood. 2011;117(2):429–39.PubMedCrossRef

36.••

Greenbaum A, Hsu YM, Day RB, Schuettpelz LG, Christopher MJ, Borgerding JN, et al. CXCL12 in early mesenchymal progenitors is required for haematopoietic stem-cell maintenance. Nature. 2013;495(7440):227–30. This article (along with Ding, 2013) demonstrated that CXCL12 produced by mesenchymal stem/progenitor cells is required for HSC maintenance and retention, while CXCL12 produced by osteoprogenitors and osteoblasts supports B lymphopoiesis.PubMedCentralPubMedCrossRef

37.•

Omatsu Y, Sugiyama T, Kohara H, Kondoh G, Fujii N, Kohno K, et al. The essential functions of adipo-osteogenic progenitors as the hematopoietic stem and progenitor cell niche. Immunity. 2010;33(3):387–99. This paper revealed that CXCL12-expressing reticular cells have osteogenic and adipogenic potential, and are required for maintenance of HSCs, lymphoid and erythroid progenitors.PubMedCrossRef

38.

Sugiyama T, Kohara H, Noda M, Nagasawa T. Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches. Immunity. 2006;25(6):977–88.PubMedCrossRef

39.

Walkley CR, Shea JM, Sims NA, Purton LE, Orkin SH. Rb regulates interactions between hematopoietic stem cells and their bone marrow microenvironment. Cell. 2007;129(6):1081–95.PubMedCentralPubMedCrossRef

40.

Park D, Spencer JA, Koh BI, Kobayashi T, Fujisaki J, Clemens TL, et al. Endogenous bone marrow MSCs are dynamic, fate-restricted participants in bone maintenance and regeneration. Cell Stem Cell. 2012;10(3):259–72.PubMedCentralPubMedCrossRef

41.•

Maes C, Kobayashi T, Selig MK, Torrekens S, Roth SI, Mackem S, et al. Osteoblast precursors, but not mature osteoblasts, move into developing and fractured bones along with invading blood vessels. Dev Cell. 2010;19(2):329–44. This article reported that osteoprogenitors are found adjacent to blood vessels in developing bone and have the capacity to migrate and differentiate into trabecular osteoblasts.PubMedCentralPubMedCrossRef

42.

Song L, Liu M, Ono N, Bringhurst FR, Kronenberg HM, Guo J. Loss of wnt/beta-catenin signaling causes cell fate shift of preosteoblasts from osteoblasts to adipocytes. J Bone Miner Res. 2012;27(11):2344–58.PubMedCentralPubMedCrossRef

43.

Liu Y, Strecker S, Wang L, Kronenberg MS, Wang W, Rowe DW, et al. Osterix-cre labeled progenitor cells contribute to the formation and maintenance of the bone marrow stroma. PLoS One. 2013;8(8):e71318.PubMedCentralPubMedCrossRef

44.

Grcevic D, Pejda S, Matthews BG, Repic D, Wang L, Li H, et al. In vivo fate mapping identifies mesenchymal progenitor cells. Stem Cells. 2012;30(2):187–96.PubMedCentralPubMedCrossRef

45.

Kalajzic Z, Li H, Wang LP, Jiang X, Lamothe K, Adams DJ, et al. Use of an alpha-smooth muscle actin GFP reporter to identify an osteoprogenitor population. Bone. 2008;43(3):501–10.PubMedCentralPubMedCrossRef

46.

Rodeheffer MS, Birsoy K, Friedman JM. Identification of white adipocyte progenitor cells in vivo. Cell. 2008;135(2):240–9.PubMedCrossRef

47.

Tang W, Zeve D, Suh JM, Bosnakovski D, Kyba M, Hammer RE, et al. White fat progenitor cells reside in the adipose vasculature. Science. 2008;322(5901):583–6.PubMedCentralPubMedCrossRef

48.

Gupta RK, Arany Z, Seale P, Mepani RJ, Ye L, Conroe HM, et al. Transcriptional control of preadipocyte determination by Zfp423. Nature. 2010;464(7288):619–23.PubMedCentralPubMedCrossRef

49.

Tran KV, Gealekman O, Frontini A, Zingaretti MC, Morroni M, Giordano A, et al. The vascular endothelium of the adipose tissue gives rise to both white and brown fat cells. Cell Metab. 2012;15(2):222–9.PubMedCentralPubMedCrossRef

50.•

Calvi LM, Bromberg O, Rhee Y, Weber JM, Smith JN, Basil MJ, et al. Osteoblastic expansion induced by parathyroid hormone receptor signaling in murine osteocytes is not sufficient to increase hematopoietic stem cells. Blood. 2012;119(11):2489–99. This article found that targeting of the constitutively active PPR to osteocytes, unlike targeting to maturing osteoblasts, fails to increase bone marow HSC frequency despite an increase in osteoblast numbers.PubMedCrossRef

51.

Calvi LM, Sims NA, Hunzelman JL, Knight MC, Giovannetti A, Saxton JM, et al. Activated parathyroid hormone/parathyroid hormone-related protein receptor in osteoblastic cells differentially affects cortical and trabecular bone. J Clin Invest. 2001;107(3):277–86.PubMedCentralPubMedCrossRef

52.

Wu J, Purton LE, Rodda SJ, Chen M, Weinstein LS, McMahon AP, et al. Osteoblastic regulation of B lymphopoiesis is mediated by Gsalpha-dependent signaling pathways. Proc Natl Acad Sci U S A. 2008;105(44):16976–81.PubMedCentralPubMedCrossRef

53.

Aguila HL, Mun SH, Kalinowski J, Adams DJ, Lorenzo JA, Lee SK. Osteoblast-specific overexpression of human interleukin-7 rescues the bone mass phenotype of interleukin-7-deficient female mice. J Bone Miner Res. 2012;27(5):1030–42.PubMedCentralPubMedCrossRef

54.•

Fulzele K, Krause DS, Panaroni C, Saini V, Barry KJ, Liu X, et al. Myelopoiesis is regulated by osteocytes through Gsalpha-dependent signaling. Blood. 2013;121(6):930–9. This article revealed a role for osteocytes in the regulation of the myeloid lineage.PubMedCrossRef

55.

Schepers K, Hsiao EC, Garg T, Scott MJ, Passegue E. Activated Gs signaling in osteoblastic cells alters the hematopoietic stem cell niche in mice. Blood. 2012;120(17):3425–35.PubMedCrossRef

56.

Peled A, Petit I, Kollet O, Magid M, Ponomaryov T, Byk T, et al. Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4. Science. 1999;283(5403):845–8.PubMedCrossRef

57.

Semerad CL, Christopher MJ, Liu F, Short B, Simmons PJ, Winkler I, et al. G-CSF potently inhibits osteoblast activity and CXCL12 mRNA expression in the bone marrow. Blood. 2005;106(9):3020–7.PubMedCrossRef

58.

Tokoyoda K, Egawa T, Sugiyama T, Choi BI, Nagasawa T. Cellular niches controlling B lymphocyte behavior within bone marrow during development. Immunity. 2004;20(6):707–18.PubMedCrossRef

59.

Blin-Wakkach C, Wakkach A, Sexton PM, Rochet N, Carle GF. Hematological defects in the oc/oc mouse, a model of infantile malignant osteopetrosis. Leukemia. 2004;18(9):1505–11.PubMedCrossRef

60.

Franzoso G, Carlson L, Xing L, Poljak L, Shores EW, Brown KD, et al. Requirement for NF-kappaB in osteoclast and B-cell development. Genes Dev. 1997;11(24):3482–96.PubMedCrossRef

61.

Kong YY, Yoshida H, Sarosi I, Tan HL, Timms E, Capparelli C, et al. OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature. 1999;397(6717):315–23.PubMedCrossRef

62.

Tagaya H, Kunisada T, Yamazaki H, Yamane T, Tokuhisa T, Wagner EF, et al. Intramedullary and extramedullary B lymphopoiesis in osteopetrotic mice. Blood. 2000;95(11):3363–70.PubMed

63.

Blin-Wakkach C, Wakkach A, Rochet N, Carle GF. Characterization of a novel bipotent hematopoietic progenitor population in normal and osteopetrotic mice. J Bone Miner Res. 2004;19(7):1137–43.PubMedCrossRef

64.

Scimeca JC, Franchi A, Trojani C, Parrinello H, Grosgeorge J, Robert C, et al. The gene encoding the mouse homologue of the human osteoclast-specific 116-kDa V-ATPase subunit bears a deletion in osteosclerotic (oc/oc) mutants. Bone. 2000;26(3):207–13.PubMedCrossRef

65.

Mansour A, Anginot A, Mancini SJ, Schiff C, Carle GF, Wakkach A, et al. Osteoclast activity modulates B-cell development in the bone marrow. Cell Res. 2011;21(7):1102–15.PubMedCrossRef

66.

Semenov M, Tamai K, He X. SOST is a ligand for LRP5/LRP6 and a Wnt signaling inhibitor. J Biol Chem. 2005;280(29):26770–5.PubMedCrossRef

67.

Cain CJ, Rueda R, McLelland B, Collette NM, Loots GG, Manilay JO. Absence of sclerostin adversely affects B-cell survival. J Bone Miner Res. 2012;27(7):1451–61.PubMedCentralPubMedCrossRef

68.

Tamura M, Sato MM, Nashimoto M. Regulation of CXCL12 expression by canonical Wnt signaling in bone marrow stromal cells. Int J Biochem Cell Biol. 2011;43(5):760–7.PubMedCrossRef

69.

Ahmed N, Khokher MA, Hassan HT. Cytokine-induced expansion of human CD34+ stem/progenitor and CD34+CD41+ early megakaryocytic marrow cells cultured on normal osteoblasts. Stem Cells. 1999;17(2):92–9.PubMedCrossRef

70.

Cheng L, Qasba P, Vanguri P, Thiede MA. Human mesenchymal stem cells support megakaryocyte and pro-platelet formation from CD34(+) hematopoietic progenitor cells. J Cell Physiol. 2000;184(1):58–69.PubMedCrossRef

71.

Avraham H, Scadden DT, Chi S, Broudy VC, Zsebo KM, Groopman JE. Interaction of human bone marrow fibroblasts with megakaryocytes: role of the c-kit ligand. Blood. 1992;80(7):1679–84.PubMed

72.

Avecilla ST, Hattori K, Heissig B, Tejada R, Liao F, Shido K, et al. Chemokine-mediated interaction of hematopoietic progenitors with the bone marrow vascular niche is required for thrombopoiesis. Nat Med. 2004;10(1):64–71.PubMedCrossRef

73.

Kacena MA, Gundberg CM, Horowitz MC. A reciprocal regulatory interaction between megakaryocytes, bone cells, and hematopoietic stem cells. Bone. 2006;39(5):978–84.PubMedCrossRef

74.

Olson TS, Caselli A, Otsuru S, Hofmann TJ, Williams R, Paolucci P, et al. Megakaryocytes promote murine osteoblastic HSC niche expansion and stem cell engraftment after radioablative conditioning. Blood. 2013;121(26):5238–49.PubMedCrossRef

75.•

Rankin EB, Wu C, Khatri R, Wilson TL, Andersen R, Araldi E, et al. The HIF signaling pathway in osteoblasts directly modulates erythropoiesis through the production of EPO. Cell. 2012;149(1):63–74. This article demonstrated that the osteoblast lineage can be a source of erythropoietin and regulate erythropoiesis.PubMedCentralPubMedCrossRef

76.

Wang Y, Wan C, Deng L, Liu X, Cao X, Gilbert SR, et al. The hypoxia-inducible factor alpha pathway couples angiogenesis to osteogenesis during skeletal development. J Clin Invest. 2007;117(6):1616–26.PubMedCentralPubMedCrossRef

Title: Mesenchymal Progenitors and the Osteoblast Lineage in Bone Marrow Hematopoietic Niches
Authors: Cristina Panaroni
Yi-shiuan Tzeng
Hamid Saeed
Joy Y. Wu
Publication date: 01-03-2014
Publisher: Springer US
Published in: Current Osteoporosis Reports / Issue 1/2014
Print ISSN: 1544-1873
Electronic ISSN: 1544-2241
DOI: https://doi.org/10.1007/s11914-014-0190-7

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Mesenchymal Progenitors and the Osteoblast Lineage in Bone Marrow Hematopoietic Niches

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2014

Vitamin D Deficiency and its Role in Muscle-Bone Interactions in the Elderly

Local Strategies to Prevent and Treat Osteoporosis

Stem Cell Therapy for Osteoporosis

Review: Epidemiology and Pathophysiology of Atypical Femur Fractures

The Role of Wnt Signaling and Sclerostin in the Pathogenesis of Glucocorticoid-Induced Osteoporosis

Osteoblast-Chondrocyte Interactions in Osteoarthritis