FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2143863472> ?p ?o ?g. }

• W2143863472 endingPage "816" @default.
• W2143863472 startingPage "809" @default.
• W2143863472 abstract "Interactions between hematopoiesis and bone metabolism have been described in various developmental and pathological situations. Here we review this evidence from the literature with a focus on microenvironmental regulation of hematopoiesis and bone metabolism. Our hypothesis is that this process occurs by bidirectional signaling between hematopoietic and mesenchymal cells through cell adhesion molecules, membrane-bound growth factors, and secreted matrix proteins. Examples of steady-state hematopoiesis and pathologies are presented and support our view that hematopoietic and mesenchymal cell functions are modulated by specific microenvironments in the bone marrow. Interactions between hematopoiesis and bone metabolism have been described in various developmental and pathological situations. Here we review this evidence from the literature with a focus on microenvironmental regulation of hematopoiesis and bone metabolism. Our hypothesis is that this process occurs by bidirectional signaling between hematopoietic and mesenchymal cells through cell adhesion molecules, membrane-bound growth factors, and secreted matrix proteins. Examples of steady-state hematopoiesis and pathologies are presented and support our view that hematopoietic and mesenchymal cell functions are modulated by specific microenvironments in the bone marrow. Bone- and blood-forming cells are closely linked within the bone marrow compartment. The formation of blood cells during hematopoiesis occurs by the commitment of hematopoietic stem cells (HSCs) into specific lineages. This process takes place in the shelter of the bone marrow, which provides protection from external threats. At the cellular level, the contribution of osteoblasts to HSC functioning [1Calvi L.M. Adams G.B. Weibrecht K.W. et al.Osteoblastic cells regulate the haematopoietic stem cell niche.Nature. 2003; 425: 841-846Crossref PubMed Scopus (2756) Google Scholar, 2Zhang J. Niu C. Ye L. et al.Identification of the haematopoietic stem cell niche and control of the niche size.Nature. 2003; 425: 836-841Crossref PubMed Scopus (2350) Google Scholar] and B-cell lymphopoiesis [3Zhu J. Garrett R. Jung Y. et al.Osteoblasts support B-lymphocyte commitment and differentiation from hematopoietic stem cells.Blood. 2007; 109: 3706-3712Crossref PubMed Scopus (272) Google Scholar] supports a model of specialized hematopoietic niches within the bone marrow. Here we review the evidence demonstrating the cross-talk between hematopoietic and mesenchymal cells, and we propose that bidirectional signaling between these two systems is essential for homeostasis. Hematopoiesis in the bone marrow proceeds from the endosteum toward the marrow cavity, with HSCs and progenitors located near the endosteum [4Lord B.I. Testa N.G. Hendr J.H. The relative spatial distribution of CFUs and CFUc in the normal mouse femur.Blood. 1975; 46: 65-72Crossref PubMed Google Scholar, 5Gong J.K. Endosteal marrow: a rich source of hematopoietic stem cells.Science. 1978; 199: 1443-1445Crossref PubMed Scopus (191) Google Scholar]. HSCs give rise to all blood cells, including T and B lymphocytes, macrophages, erythrocytes, megakaryocytes, and granulocytes. HSCs with the greatest hematopoietic reconstitutive potential are located near the endosteum [6Haylock D.N. Williams B. Johnston H.M. et al.Hemopoietic stem cells with higher hemopoietic potential reside at the bone marrow endosteum.Stem Cells. 2007; 25: 1062-1069Crossref PubMed Scopus (98) Google Scholar], and quiescent, long-term reconstitutive HSCs are located in hypoxic regions of the marrow [7Winkler I.G. Barbier V. Wadley R. Zannettino A.C.W. Williams S. Lévesque J.-P. Positioning of bone marrow hematopoietic and stromal cells relative to blood flow in vivo: serially reconstituting hematopoietic stem cells reside in distinct nonperfused niches.Blood. 2010; 116: 375-385Crossref PubMed Scopus (186) Google Scholar]. In contrast, mesenchymal stem cells (MSCs) are located in high-oxygen regions within the marrow, supporting the perivascular localization hypothesis [7Winkler I.G. Barbier V. Wadley R. Zannettino A.C.W. Williams S. Lévesque J.-P. Positioning of bone marrow hematopoietic and stromal cells relative to blood flow in vivo: serially reconstituting hematopoietic stem cells reside in distinct nonperfused niches.Blood. 2010; 116: 375-385Crossref PubMed Scopus (186) Google Scholar, 8Shi S. Gronthos S. Perivascular niche of postnatal mesenchymal stem cells in human bone marrow and dental pulp.J Bone Miner Res. 2003; 18: 696-704Crossref PubMed Scopus (1122) Google Scholar]. MSCs give rise to mature mesenchymal cells, including osteoblasts, adipocytes, connective tissue stromal cells, and chondrocytes, which are all necessary to form the skeleton (reviewed in [9Dennis J.E. Charbord P. Origin and differentiation of human and murine stroma.Stem Cells. 2002; 20: 205-214Crossref PubMed Scopus (284) Google Scholar]). Oxygen tension is a determinant for heterotrophic bone formation, and an initial low-oxygen microenvironment is essential for further bone formation [10Olmsted-Davis E. Gannon F.H. Ozen M. et al.Hypoxic adipocytes pattern early heterotopic bone formation.Am J Pathol. 2007; 170: 620-632Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar, 11Fouletier Dilling C. Wada A.M. Lazard Z.W. et al.Vessel formation is induced prior to the appearance of cartilage in BMP-2-mediated heteropic ossification.J Bone Miner Res. 2010; 25: 1147-1156PubMed Google Scholar]. This suggests that discrete microenvironments that drive the differentiation of hematopoietic and mesenchymal cells exist within the marrow cavity. A stem cell follows a specific developmental pathway during maturation. Intrinsic transcriptional regulators and extrinsic signals, such as growth factors, regulate development. In this review, we will focus on the nonautonomous control of development, which relies on external factors provided by the microenvironment. In this scenario, the fate of the daughter cells resulting from stem cell division is affected by the microenvironment in an instructive fashion. Specifically, the spatial localization of the stem cell within the specialized microenvironment influences the fate of the daughter cells [12Morrison S.J. Shah N.M. Anderson D.J. Regulatory mechanisms in stem cell biology.Cell. 1997; 88: 287-298Abstract Full Text Full Text PDF PubMed Scopus (880) Google Scholar]. This is the concept of a niche, originally proposed by Schofield [13Schofield R. The relationship between the spleen colony-forming cell and the hematopoietic stem cell.Blood Cells. 1978; 4: 7-25PubMed Google Scholar]. A key component of the niche is the mesenchymal cell, which produces extracellular matrix components and growth factors and also actively retains hematopoietic cells by expressing adhesion molecules. Together, these extracellular matrix proteins and secreted growth factors, as well as the membrane-bound growth factors and adhesion molecules expressed by mesenchymal cells, provide signals to and regulate the fate of the hematopoietic cells. Thus, it is logical to view the niche not only as a recipient for hematopoietic cells, but also as a dynamic environment that responds to hematopoietic cell contact (Fig. 1A ). In our opinion, the bidirectional signaling between mesenchymal and hematopoietic cells is essential for the maintenance of both bone metabolism and hematopoiesis in the marrow cavity (Fig. 1B). Here, we review examples of this bidirectional regulation at the cellular level and in vivo interactions between hematopoiesis and bone metabolism, which support our hypothesis. Cell types discussed in this review are presented in Table 1. Because recent excellent recent reviews have addressed in detail the role of adipocytes and B/T lymphocytes on bone metabolism [19Muruganandan S. Roman A.A. Sinal C.J. Adipocyte differentiation of bone marrow-derived mesenchymal stem cells: cross talk with the osteoblastogenic program.Cell Mol Life Sci. 2009; 66: 236-253Crossref PubMed Scopus (349) Google Scholar, 20Pacifici R. T cells: critical bone regulators in health and disease.Bone. 2010; 47: 461-471Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar, 21Horowitz M.C. Fretz J.A. Lorenzo J.A. How B cells influence bone biology in health and disease.Bone. 2010; 47: 472-479Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar], we focused our attention on interactions among bone cells, HSCs, and myeloid cells. Although these interactions among bone cells, HSCs, and myeloid cells have been documented in vitro, studies on myeloid pathologies, such as myelodysplatic syndromes (MDS), myeloid leukemias, and myeloproliferative diseases (MPDs), help to further characterize the contribution of bone cells in the disease progression, supporting the concept of bidirectional interactions between bone metabolism and hematopoiesis.Table 1Functions of the cell typesCell typesFunctionsReferencesMesenchymal cellsMesenchymal stem cellsGive rise to osteoblasts, chondrocytes, adipocytesReviewed in 9Dennis J.E. Charbord P. Origin and differentiation of human and murine stroma.Stem Cells. 2002; 20: 205-214Crossref PubMed Scopus (284) Google ScholarOsteoprogenitorsCells committed in the osteogenic lineageReviewed in 9Dennis J.E. Charbord P. Origin and differentiation of human and murine stroma.Stem Cells. 2002; 20: 205-214Crossref PubMed Scopus (284) Google ScholarOsteoblastsBone matrix producing cellsReviewed in 9Dennis J.E. Charbord P. Origin and differentiation of human and murine stroma.Stem Cells. 2002; 20: 205-214Crossref PubMed Scopus (284) Google ScholarHematopoietic cellsHematopoietic stem cellsGive rise to all blood cell typesReviewed in 14Zon L.I. Intrinsic and extrinsic control of haematopoietic stem-cell self-renewal.Nature. 2008; 453: 306-313Crossref PubMed Scopus (223) Google ScholarMyeloid progenitorsCells committed to the myeloid lineageReviewed in 15Iwasaki H. Akashi K. Myeloid lineage commitment from the hematopoietic stem cell.Immunity. 2007; 26: 726-740Abstract Full Text Full Text PDF PubMed Scopus (280) Google ScholarMegakaryocytesPlatelet-producing cellsReviewed in 16Geddis A.E. Megakaryopoiesis.Semin Hematol. 2010; 47: 212-219Abstract Full Text Full Text PDF PubMed Scopus (80) Google ScholarMonocytesBlood circulating phagocytesReviewed in 17Dale D.C. Boxer L. Liles W.C. The phagocytes: neutrophils and monocytes.Blood. 2008; 112: 935-945Crossref PubMed Scopus (482) Google ScholarOsteoclast precursorsMyeloid cells committed to the osteoclast lineageReviewed in 18Teitelbaum S.L. Ross F.P. Genetic regulation of osteoclast development and function.Nat Rev Genet. 2003; 4: 638-649Crossref PubMed Scopus (1269) Google ScholarOsteoclastsBone-resorbing cellsReviewed in 18Teitelbaum S.L. Ross F.P. Genetic regulation of osteoclast development and function.Nat Rev Genet. 2003; 4: 638-649Crossref PubMed Scopus (1269) Google Scholar Open table in a new tab An example of the interplay between mesenchymal and hematopoietic cells is provided by the osteoclast, a multinucleated cell arising from the fusion of monocyte precursors and the only known bone-resorbing cell. The differentiation of mature osteoclasts from precursors is dependent on their interactions with osteoblasts because the ablation of mature osteoblasts is sufficient to abrogate osteoclastogenesis in vivo [22Visnjic D. Kalajzic I. Gronowicz G. et al.Conditional ablation of the osteoblast lineage in Col2.3Δtk transgenic mice.J Bone Miner Res. 2001; 16: 2222-2231Crossref PubMed Scopus (92) Google Scholar, 23Visnjic D. Kalajzic Z. Rowe D.W. Katavic V. Lorenzo J. Aguila H.L. Hematopoiesis is severely altered in mice with an induced osteoblast deficiency.Blood. 2004; 103: 3258-3264Crossref PubMed Scopus (584) Google Scholar]. The osteoblast produces the key osteoclastogenic cytokines, macrophage colony-stimulating factor and receptor activator of nuclear factor κB ligand (RANKL), which play an essential instructive role in the commitment of monocytic cells into osteoclast precursors [24Yoshida H. Hayashi S.-I. Kunisada T. et al.The murine mutation osteopetrosis is in the coding region of the macrophage colony stimulating factor gene.Nature. 1990; 345: 442-444Crossref PubMed Scopus (1491) Google Scholar, 25Kong Y.-Y. Yoshida H. Sarosi I. et al.OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis.Nature. 1999; 397: 315-323Crossref PubMed Scopus (2796) Google Scholar]. The bidirectional signals between osteoclasts and osteoblasts modulate the function of these two cell types. Osteoclast activity is induced by adhesion to bone through integrin αvβ3, which leads to polarization of the cell and the formation of the ruffled border necessary for bone degradation [26Ross F.P. Teitelbaum S.L. αvβ3 and macrophage colony-stimulating factor: partners in osteoclast biology.Immunol Rev. 2005; 208: 88-105Crossref PubMed Scopus (252) Google Scholar]. Bone-resorbing activity is also enhanced by pro-resorption cytokines, such as interleukin-6, interleukin-1β, and tumor necrosis factor−α [27Takayanagi H. Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems.Nat Rev Immunol. 2007; 7: 292-304Crossref PubMed Scopus (1279) Google Scholar]. The bone-resorbing activity of osteoclasts, in turn, activates bone formation by osteoblasts. The coupling of the bone resorption and formation activities of these two cell types, which together form the bone-remodeling system, ensures the maintenance of bone metabolism. An imbalance in either bone resorption or formation leads to bone pathologies, such as osteoporosis. The HSC population of the marrow is maintained during the entire life of an individual through a delicate balance between self-renewal and expansion to prevent exhaustion of the population. At the cellular level, HSCs can either become quiescent, maintaining their HSC properties and population size for later in life, or become proliferative to meet the needs of the organism in case of pathologies. The balance between the cell autonomous control of quiescence and self-renewal has been shown to rely on external factors provided by the niche. The HSC niche represents the best-characterized model of a niche in mammals (reviewed in [28Kiel M.J. Morrison S.J. Uncertainty in the niches that maintain haematopoietic stem cells.Nat Rev Immunol. 2008; 290: 290-301Crossref Scopus (465) Google Scholar]). HSCs have been observed in close contact with both osteoblasts in vivo [1Calvi L.M. Adams G.B. Weibrecht K.W. et al.Osteoblastic cells regulate the haematopoietic stem cell niche.Nature. 2003; 425: 841-846Crossref PubMed Scopus (2756) Google Scholar, 29Arai F. Hirao A. Ohmura M. et al.Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche.Cell. 2004; 118: 149-161Abstract Full Text Full Text PDF PubMed Scopus (1510) Google Scholar] and sinusoidal endothelial cells of the marrow [30Kiel M.J. Yilmaz ÖH. Iwashita T. Yilmaz O.H. Terhorst, Morrison SJ. SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells.Cell. 2005; 121: 1109-1121Abstract Full Text Full Text PDF PubMed Scopus (2359) Google Scholar], suggesting the existence of at least two specialized microenvironments within the marrow. The formation of hematopoietic clusters near bone marrow sinusoids after myeloablation is indirect evidence of the proliferative support of the endothelial niche [31Heissig B. Hattori K. Dias S. et al.Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of Kit-ligand.Cell. 2002; 109: 625-637Abstract Full Text Full Text PDF PubMed Scopus (1491) Google Scholar], suggesting that HSCs located near sinusoids can be rapidly mobilized in the circulation during stress. Furthermore, endothelial cells promote HSC proliferation in vitro and maintain their reconstitutive potential in vivo [32Butler J.M. Nolan D.J. Vertes E. et al.Endothelial cells are essential for the self-renewal and repopulation of Notch-dependent hematopoietic stem cells.Cell Stem Cell. 2010; 6: 251-264Abstract Full Text Full Text PDF PubMed Scopus (475) Google Scholar]. The interactions between endothelial cells expressing P- and E-selectins and HSCs expressing E-selectin ligand and CD62L could regulate this process. Indeed, culturing HSCs with soluble P-selectin and growth factors delays the differentiation of hematopoietic progenitors and promotes expansion in vitro [33Eto T. Winkler I. Purton L.E. Lévesque J.P. Contrasting effects of P-selectin and E-selectin on the differentiation of murine hematopoietic progenitor cells.Exp Hematol. 2005; 33: 232-242Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar]. There is evidence that the vascular niche could also include interactions between MSCs, osteoprogenitor cells, and HSCs. Capillaries are formed from a single layer of vascular endothelial cells, while medium-sized and large vessels are surrounded by mural cells, such as pericytes and smooth muscle cells, which provide a stronger structure to the vessels [34Carmeliet P. Angiogenesis in health and disease.Nat Med. 2003; 9: 653-660Crossref PubMed Scopus (3393) Google Scholar]. Among the cell types closely associated with vessels are MSCs and osteoprogenitors. In fact, osteoprogenitors are located near vascular pericytes, which may explain the osteogenic potential of bovine vascular pericytes [35Doherty M.J. Ashton B.A. Walsh S. Beresford J.N. Grant M.E. Canfield A.E. Vascular pericytes express osteogenic potential in vitro and in vivo.J Bone Miner Res. 1998; 13: 828-838Crossref PubMed Scopus (461) Google Scholar]. In the mouse model, an osteoprogenitor population expressing α-smooth muscle actin, a marker of smooth muscle cells and pericytes, is amplified in vivo after depletion of mature osteoblasts [36Kalajzic I. Kalajzic Z. Wang L. et al.Pericyte/myofibroblast phenotype of osteoprogenitor cell.J Musculoskelet Neuronal Interact. 2007; 7: 320-322PubMed Google Scholar, 37Kalajzic Z. Li H. Wang L.P. et al.Use of an alpha-smooth muscle actin GFP reporter to identify an osteoprogenitor population.Bone. 2008; 43: 501-510Abstract Full Text Full Text PDF PubMed Scopus (127) Google Scholar]. This osteoprogenitor population is found in perivascular areas and endocortical surfaces. Furthermore, a human osteoprogenitor population defined by the expression of melanoma cell adhesion molecule/CD146 showed both mural cell and osteoblast potential in vitro and in vivo [38Sacchetti B. Funari A. Michienzi S. et al.Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment.Cell. 2007; 131: 324-336Abstract Full Text Full Text PDF PubMed Scopus (1648) Google Scholar]. Recruitment of HSCs may also result from the local production of secreted factors and expression of adhesion molecules in response to the presence of other cell types in the vicinity of blood vessels, such as osteoprogenitors and MSCs. Consistent with this hypothesis, MSCs that are located near endothelial cells of the marrow interact with HSCs, thereby promoting their maintenance in the marrow [39Méndez-Ferrer S. Michurina T.V. Ferraro F. et al.Mesenchymal and haematopoietic stem cells form a unique bone marrow niche.Nature. 2010; 466: 829-834Crossref PubMed Scopus (2368) Google Scholar]. A molecular analysis of osteoblasts supports the view that the bone marrow niche maintains HSC quiescence (Fig. 1B), indicating that long-term reconstitutive HSCs are localized in the endosteal niche. Because osteoblasts express thrombopoietin, angiopoietin-1, and osteopontin, it is likely that these factors regulate HSC quiescence, although other cell types, including macrophages, also produce these factors [29Arai F. Hirao A. Ohmura M. et al.Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche.Cell. 2004; 118: 149-161Abstract Full Text Full Text PDF PubMed Scopus (1510) Google Scholar, 40Yoshihara H. Arai F. Hosokawa K. et al.Thrombopoietin/MPL signaling regulates hematopoietic stem cell quiescence and interaction with the osteoblastic niche.Cell Stem Cell. 2007; 1: 685-697Abstract Full Text Full Text PDF PubMed Scopus (551) Google Scholar, 41Nilsson S.K. Johnston H.M. Whitty G.A. et al.Osteopontin, a key component of the hematopoietic stem cell niche and regulator of primitive hematopoietic progenitor cells.Blood. 2005; 106: 1232-1239Crossref PubMed Scopus (593) Google Scholar, 42Stier S. Ko Y. Forkert R. et al.Osteopontin is a hematopoietic stem cell niche component that negatively regulated stem cell pool size.J Exp Med. 2005; 201: 1781-1791Crossref PubMed Scopus (521) Google Scholar]. Cell adhesion molecules also play a central role in this process. For example, the binding of osteopontin to HSCs is mediated by very late antigen (VLA)−4 and α9β1 integrin [43Grassinger J. Haylock D.N. Storan M.J. et al.Thrombin-cleaved osteopontin regulates hemopoetic stem and progenitor cell functions through interactions with alpha9beta1 and alpha4beta1 integrins.Blood. 2009; 114: 49-59Crossref PubMed Scopus (149) Google Scholar] (Fig. 1B). Other cell-surface adhesion molecules that could regulate interactions between osteoblasts and HSCs include N-cadherins (Fig. 1B), although their contribution is a matter of controversy. In fact, whether N-cadherin is expressed on the surface of HSCs remains unclear [2Zhang J. Niu C. Ye L. et al.Identification of the haematopoietic stem cell niche and control of the niche size.Nature. 2003; 425: 836-841Crossref PubMed Scopus (2350) Google Scholar, 44Kiel M.J. Radice G.L. Morrison S.J. Lack of evidence that hematopoietic stem cells depend on N-cadherin-mediated adhesion to osteoblasts for their maintenance.Cell Stem Cell. 2007; 1: 204-207Abstract Full Text Full Text PDF PubMed Scopus (250) Google Scholar, 45Haug J.S. He X.C. Grindley J.C. et al.N-cadherin expression level distingues reserved versus primed states of hematopoietic stem cells.Cell Stem Cell. 2008; 2: 367-379Abstract Full Text Full Text PDF PubMed Scopus (115) Google Scholar]. In addition, although genetic ablation of N-cadherin failed to provide evidence for their role in regulating interactions between osteoblasts and HSCs [46Kiel M.J. Acar M. Radice G.L. Morrison S.J. Hematopoietic stem cells do not depend on N-cadherin to regulate their maintenance.Cell Stem Cell. 2009; 4: 170-179Abstract Full Text Full Text PDF PubMed Scopus (142) Google Scholar], other experiments support the possibility that N-cadherin is necessary for the reconstitutive potential [47Hosokawa K. Arai F. Yoshihara H. et al.Knockdown of N-cadherin suppresses the long-term engraftment of hematopoietic stem cells.Blood. 2010; 116: 554-563Crossref PubMed Scopus (94) Google Scholar]. The expression of vascular cell adhesion molecule−1 and intercellular adhesion molecule−1 (ICAM-1) by HSCs is also important for their survival [48Jung Y. Wang J. Havens A. et al.Cell-to-cell contact is critical for the survival of hematopoietic progenitor cells on osteoblasts.Cytokine. 2005; 32: 155-162Crossref PubMed Scopus (63) Google Scholar]. Altogether, these results indicate that osteoblasts can regulate HSC function by cell-to-cell interactions mediated through adhesion molecules and secretion of matrix proteins (Fig. 1B). In line with this, an increase in osteoblast activity in vivo leads to expansion of the HSC population [1Calvi L.M. Adams G.B. Weibrecht K.W. et al.Osteoblastic cells regulate the haematopoietic stem cell niche.Nature. 2003; 425: 841-846Crossref PubMed Scopus (2756) Google Scholar, 2Zhang J. Niu C. Ye L. et al.Identification of the haematopoietic stem cell niche and control of the niche size.Nature. 2003; 425: 836-841Crossref PubMed Scopus (2350) Google Scholar]. Conversely, a loss of bone mass due to specific deletion of osteoblasts causes HSC relocation to the spleen and liver [22Visnjic D. Kalajzic I. Gronowicz G. et al.Conditional ablation of the osteoblast lineage in Col2.3Δtk transgenic mice.J Bone Miner Res. 2001; 16: 2222-2231Crossref PubMed Scopus (92) Google Scholar, 23Visnjic D. Kalajzic Z. Rowe D.W. Katavic V. Lorenzo J. Aguila H.L. Hematopoiesis is severely altered in mice with an induced osteoblast deficiency.Blood. 2004; 103: 3258-3264Crossref PubMed Scopus (584) Google Scholar], demonstrating the crucial role of osteoblasts in retaining HSCs within the marrow. Finally, osteoclastogenesis can also regulate the HSC niche. Following the specific deletion of osteoblasts, a simultaneous loss of osteoclast precursors, mature osteoclasts, and HSCs was observed in the bone marrow [22Visnjic D. Kalajzic I. Gronowicz G. et al.Conditional ablation of the osteoblast lineage in Col2.3Δtk transgenic mice.J Bone Miner Res. 2001; 16: 2222-2231Crossref PubMed Scopus (92) Google Scholar, 23Visnjic D. Kalajzic Z. Rowe D.W. Katavic V. Lorenzo J. Aguila H.L. Hematopoiesis is severely altered in mice with an induced osteoblast deficiency.Blood. 2004; 103: 3258-3264Crossref PubMed Scopus (584) Google Scholar], suggesting a contribution of precursors and mature osteoclasts in retaining HSCs. Various osteoclast precursors and macrophage populations could contribute to this process. A specific loss of a macrophage subpopulation does indeed lead to egress of HSCs following granulocyte colony-stimulating factor treatment, without affecting mature osteoclast populations [49Winkler I.G. Sims N.A. Pettit A.R. et al.Bone marrow macrophages maintain hematopoietic stem cell (HSC) niches and their depletion mobilizes HSC.Blood. 2010; 116: 4815-4828Crossref PubMed Scopus (573) Google Scholar]. These results suggest a role for osteoclast precursors in retaining HSCs in the marrow. Mature osteoclasts also contribute to the retention of quiescent HSCs in the marrow. Inhibition of osteoclast function led to decreased number and increased cycling of HSCs [50Lymperi S. Ersek A. Ferraro F. Dazzi F. Horwood N.J. Inhibition of osteoclast function reduces hematopoietic stem cell numbers in vivo.Blood. 2011; 117: 1540-1549Crossref PubMed Scopus (101) Google Scholar]. However, specific activation of osteoclast activity by RANKL treatment leads to mobilization of immature hematopoietic progenitor cells into the blood [51Kollet O. Dar A. Shivtiel S. et al.Osteoclasts degrade endosteal components and promote mobilization of hematopoietic progenitor cells.Nat Med. 2006; 12: 657-664Crossref PubMed Scopus (613) Google Scholar]. Furthermore, the treatment of mice with calcitonin, an inhibitor of osteoclast function, reversed the effects of granulocyte colony-stimulating factor−induced hematopoietic progenitor cell mobilization [51Kollet O. Dar A. Shivtiel S. et al.Osteoclasts degrade endosteal components and promote mobilization of hematopoietic progenitor cells.Nat Med. 2006; 12: 657-664Crossref PubMed Scopus (613) Google Scholar]. Taken together, these studies support the view that macrophages, osteoclast precursors, and mature osteoclasts regulate the HSC niche. Platelet formation is tightly regulated at the cellular level by the transcription factors nuclear factor (erythroid-derived 2) and GATA-1. Genetic deletion of these genes, which abrogates megakaryocytopoiesis, reveals a cross-talk between bone cells, endothelial cells, and megakaryocytes (MKs). MKs appear to modulate osteoblast proliferation by cell-to-cell contact because osteoblasts cultured with MKs showed increased proliferation in cocultures, but not in transwell experiments [52Kacena M.A. Shivdasani R.A. 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: 652-660Crossref PubMed Scopus (115) Google Scholar]. Integrins expressed on MKs, including α3, α5, and αIIb, are necessary for this proliferative effect on osteoblasts [53Lemieux J.M. Horowitz M.C. Kacena M.A. Involvement of integrins α3β1 and α5β1 and glycoprotein IIb in megakaryocyte-induced osteoblast proliferation.J Cell Biochem. 2010; 109: 927-932PubMed Google Scholar]. Furthermore, MKs also secrete factors that inhibit osteoblast proliferation, as shown in MK-conditioned medium experiments [52Kacena M.A. Shivdasani R.A. 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: 652-660Crossref PubMed Scopus (115) Google Scholar]. In turn, osteoblasts regulate megakaryocytopoiesis through expression of thrombopoietin, the growth factor essential for initiating platelet formation [40Yoshihara H. Arai F. Hosokawa K. et al.Thrombopoietin/MPL signaling regulates hematopoietic stem cell quiescence and interaction with the osteoblastic niche.Cell Stem Cell. 2007; 1: 685-697Abstract Full Text Full Text PDF PubMed Scopus (551) Google Scholar]. Megakaryocytopoiesis may also involve bone marrow endothelial cells, which have been shown to support megakaryocytopoiesis when cocultured with hematopoietic progenitors [54Rafii S. Shapiro F. Pettengell R. et al.Human bone marrow microvascular endothelial cells support long-term proliferation and differentiation of myeloid and megakaryocytic progenitors.Blood. 1995; 86: 3353-3363PubMed Google Scholar]. Direct contact between endothelial cells and hematopoietic cells was essential to effectively promote megakaryocytopoiesis in vitro [54Rafii S. Shapiro F. Pettengell R. et al.Human bone marrow microvascular endothelial cells support long-term proliferation and differentiation of myeloid and megakaryocytic progenitors.Blood. 1995; 86: 3353-3363PubMed Google Scholar]. In fact, the maturation of MKs is thrombopoietin-independent and relies on sinusoidal endothelial cells [55Avecilla S.T. Hattori K. Heissig B. et al.Chemokine-mediated interaction of hema" @default.
• W2143863472 created "2016-06-24" @default.
• W2143863472 creator A5003322324 @default.
• W2143863472 creator A5065466733 @default.
• W2143863472 date "2011-08-01" @default.
• W2143863472 modified "2023-10-16" @default.
• W2143863472 title "Bidirectional interactions between bone metabolism and hematopoiesis" @default.
• W2143863472 cites W1534645474 @default.
• W2143863472 cites W1561399318 @default.
• W2143863472 cites W1838439206 @default.
• W2143863472 cites W1965107300 @default.
• W2143863472 cites W1968628080 @default.
• W2143863472 cites W1969726379 @default.
• W2143863472 cites W1971987125 @default.
• W2143863472 cites W1973157096 @default.
• W2143863472 cites W1973853319 @default.
• W2143863472 cites W1975025595 @default.
• W2143863472 cites W1975247371 @default.
• W2143863472 cites W1978598034 @default.
• W2143863472 cites W1981514467 @default.
• W2143863472 cites W1981884992 @default.
• W2143863472 cites W1985753831 @default.
• W2143863472 cites W1989172510 @default.
• W2143863472 cites W1990792003 @default.
• W2143863472 cites W1993789974 @default.
• W2143863472 cites W1993959445 @default.
• W2143863472 cites W1994294560 @default.
• W2143863472 cites W1995827857 @default.
• W2143863472 cites W1997184614 @default.
• W2143863472 cites W1999156648 @default.
• W2143863472 cites W1999619355 @default.
• W2143863472 cites W2001189096 @default.
• W2143863472 cites W2011174877 @default.
• W2143863472 cites W2012326387 @default.
• W2143863472 cites W2017907565 @default.
• W2143863472 cites W2018420076 @default.
• W2143863472 cites W2019524333 @default.
• W2143863472 cites W2021276131 @default.
• W2143863472 cites W2024932182 @default.
• W2143863472 cites W2026501903 @default.
• W2143863472 cites W2030508471 @default.
• W2143863472 cites W2033962350 @default.
• W2143863472 cites W2037072015 @default.
• W2143863472 cites W2037736150 @default.
• W2143863472 cites W2040662877 @default.
• W2143863472 cites W2041138285 @default.
• W2143863472 cites W2041590882 @default.
• W2143863472 cites W2042095186 @default.
• W2143863472 cites W2049231184 @default.
• W2143863472 cites W2049869441 @default.
• W2143863472 cites W2053899257 @default.
• W2143863472 cites W2054516994 @default.
• W2143863472 cites W2056449496 @default.
• W2143863472 cites W2060610551 @default.
• W2143863472 cites W2061968656 @default.
• W2143863472 cites W2063626613 @default.
• W2143863472 cites W2064574476 @default.
• W2143863472 cites W2069452246 @default.
• W2143863472 cites W2070793750 @default.
• W2143863472 cites W2073287109 @default.
• W2143863472 cites W2074624875 @default.
• W2143863472 cites W2076974856 @default.
• W2143863472 cites W2077330278 @default.
• W2143863472 cites W2077891477 @default.
• W2143863472 cites W2078489918 @default.
• W2143863472 cites W2078623934 @default.
• W2143863472 cites W2081408582 @default.
• W2143863472 cites W2088022688 @default.
• W2143863472 cites W2088690702 @default.
• W2143863472 cites W2091637866 @default.
• W2143863472 cites W2100063372 @default.
• W2143863472 cites W2102876135 @default.
• W2143863472 cites W2105797231 @default.
• W2143863472 cites W2108585990 @default.
• W2143863472 cites W2109525494 @default.
• W2143863472 cites W2114736117 @default.
• W2143863472 cites W2114842626 @default.
• W2143863472 cites W2120372000 @default.
• W2143863472 cites W2123463315 @default.
• W2143863472 cites W2125410884 @default.
• W2143863472 cites W2130443006 @default.
• W2143863472 cites W214380766 @default.
• W2143863472 cites W2147970485 @default.
• W2143863472 cites W2153503145 @default.
• W2143863472 cites W2156554521 @default.
• W2143863472 cites W2157155777 @default.
• W2143863472 cites W2167812891 @default.
• W2143863472 cites W4211114385 @default.
• W2143863472 cites W4211209311 @default.
• W2143863472 cites W4229977181 @default.
• W2143863472 cites W4241182814 @default.
• W2143863472 doi "https://doi.org/10.1016/j.exphem.2011.04.008" @default.
• W2143863472 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21609752" @default.
• W2143863472 hasPublicationYear "2011" @default.
• W2143863472 type Work @default.
• W2143863472 sameAs 2143863472 @default.
• W2143863472 citedByCount "11" @default.
• W2143863472 countsByYear W21438634722012 @default.

• next