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Current Osteoporosis Reports
Published in: Current Osteoporosis Reports 2/2013

01-06-2013 | Skeletal Biology (DB Burr, Section Editor)

The Changing Balance Between Osteoblastogenesis and Adipogenesis in Aging and its Impact on Hematopoiesis

Authors: Monique Bethel, Brahmananda R. Chitteti, Edward F. Srour, Melissa A. Kacena

Published in: Current Osteoporosis Reports | Issue 2/2013

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Abstract

Osteoblasts (OBs) and adipocytes (APs) share a common mesenchymal ancestor. It is now clear that mesenchymal stem cell (MSC) maturation along the OB lineage comes at the expense of adipogenesis and vice versa. During aging, this balance increasingly favors the formation of APs. Hematopoiesis also slowly declines during the aging process. The role of OB lineage cells in hematopoiesis has been studied, but less is known about how APs regulate hematopoiesis. A few studies have demonstrated a negative relationship between APs and hematopoiesis; however, there is also evidence that brown adipose tissue (BAT) may promote hematopoiesis. This review will examine the current knowledge of how adipogenesis and osteogenesis change with aging and the implications of this changing environment on hematopoeisis.
Literature
1.
Zafon C. Oscillations in total body fat content through life: an evolutionary perspective. Obes Rev. 2007;8:525–30.PubMedCrossRef
2.
3.
Warren LA, Rossi DJ. Stem cells and aging in the hematopoietic system. Mech Ageing Dev. 2009;130:46–53.PubMedCrossRef
4.
Justesen J, Stenderup K, Ebbesen EN, et al. Adipocyte tissue volume in bone marrow is increased with aging and in patients with osteoporosis. Biogerontology. 2001;2:165–71.PubMedCrossRef
5.
Giordano A, Cesari P, Capparuccia L, et al. Sema3A and neuropilin-1 expression and distribution in rat white adipose tissue. J Neurocytol. 2003;32:345–52.PubMedCrossRef
6.
Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284:143–7.PubMedCrossRef
7.
Otto F, Thornell AP, Crompton T, et al. Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development. Cell. 1997;89:765–71.PubMedCrossRef
8.
Marie PJ. Transcription factors controlling osteoblastogenesis. Arch Biochem Biophys. 2008;473:98–105.PubMedCrossRef
9.
Fajas L, Fruchart JC, Auwerx J. Transcriptional control of adipogenesis. Curr Opin Cell Biol. 1998;10:165–73.PubMedCrossRef
10.
Lin GL, Hankenson KD. Integration of BMP, Wnt, and notch signaling pathways in osteoblast differentiation. J Cell Biochem. 2011;112:3491–501.PubMedCrossRef
11.
12.
Ross SE, Hemati N, Longo KA, et al. Inhibition of adipogenesis by Wnt signaling. Science. 2000;289:950–3.PubMedCrossRef
13.
Liu J, Farmer SR. Regulating the balance between peroxisome proliferator-activated receptor gamma and beta-catenin signaling during adipogenesis. A glycogen synthase kinase 3beta phosphorylation-defective mutant of beta-catenin inhibits expression of a subset of adipogenic genes. J Biol Chem. 2004;279:45020–7.PubMedCrossRef
14.
Cawthon PM. Gender differences in osteoporosis and fractures. Clin Orthop Relat Res. 2011;469:1900–5.PubMedCrossRef
15.
Seeman E. Invited review: pathogenesis of osteoporosis. J Appl Physiol. 2003;95:2142–51.PubMed
16.
Modder UI, Roforth MM, Nicks KM, et al. Characterization of mesenchymal progenitor cells isolated from human bone marrow by negative selection. Bone. 2012;50:804–10.PubMedCrossRef
17.
D'Ippolito G, Schiller PC, Ricordi C, et al. Age-related osteogenic potential of mesenchymal stromal stem cells from human vertebral bone marrow. J Bone Miner Res. 1999;14:1115–22.PubMedCrossRef
18.
Zhou S, Greenberger JS, Epperly MW, et al. Age-related intrinsic changes in human bone-marrow-derived mesenchymal stem cells and their differentiation to osteoblasts. Aging Cell. 2008;7:335–43.PubMedCrossRef
19.
Nishida S, Endo N, Yamagiwa H, et al. Number of osteoprogenitor cells in human bone marrow markedly decreases after skeletal maturation. J Bone Miner Metab. 1999;17:171–7.PubMedCrossRef
20.
Kuznetsov SA, Mankani MH, Bianco P, et al. Enumeration of the colony-forming units-fibroblast from mouse and human bone marrow in normal and pathological conditions. Stem Cell Res. 2009;2:83–94.PubMedCrossRef
21.
Stenderup K, Justesen J, Clausen C, et al. Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells. Bone. 2003;33:919–26.PubMedCrossRef
22.
Rauner M, Sipos W, Pietschmann P. Age-dependent Wnt gene expression in bone and during the course of osteoblast differentiation. Age. 2008;30:273–82.PubMedCrossRef
23.
Essers MA, de Vries-Smits LM, Barker N, et al. Functional interaction between beta-catenin and FOXO in oxidative stress signaling. Science. 2005;308:1181–4.PubMedCrossRef
24.
Almeida M, Han L, Martin-Millan M, et al. Oxidative stress antagonizes Wnt signaling in osteoblast precursors by diverting beta-catenin from T cell factor- to forkhead box O-mediated transcription. J Biol Chem. 2007;282:27298–305.PubMedCrossRef
25.
Chang S, Multani AS, Cabrera NG, et al. Essential role of limiting telomeres in the pathogenesis of Werner syndrome. Nat Genet. 2004;36:877–82.PubMedCrossRef
26.
Du X, Shen J, Kugan N, et al. Telomere shortening exposes functions for the mouse Werner and Bloom syndrome genes. Mol Cell Biol. 2004;24:8437–46.PubMedCrossRef
27.
Pignolo RJ, Suda RK, McMillan EA, et al. Defects in telomere maintenance molecules impair osteoblast differentiation and promote osteoporosis. Aging Cell. 2008;7:23–31.PubMedCrossRef
28.
Saeed H, Abdallah BM, Ditzel N, et al. Telomerase-deficient mice exhibit bone loss owing to defects in osteoblasts and increased osteoclastogenesis by inflammatory microenvironment. J Bone Miner Res. 2011;26:1494–505.PubMedCrossRef
29.
Simonsen JL, Rosada C, Serakinci N, et al. Telomerase expression extends the proliferative life-span and maintains the osteogenic potential of human bone marrow stromal cells. Nat Biotechnol. 2002;20:592–6.PubMedCrossRef
30.
• Wang H, Chen Q, Lee SH, et al. Impairment of osteoblast differentiation due to proliferation-independent telomere dysfunction in mouse models of accelerated aging. Aging Cell. 2012;11:704–13. This study highlights how processes common in aging males and females can inhibit osteoblastogenesis and thus bone formation, helping shift the focus away from the estrogen deficiency model of osteoporosis.PubMedCrossRef
31.
Ding SL, Shen CY. Model of human aging: recent findings on Werner's and Hutchinson-Gilford progeria syndromes. Clin Interv Aging. 2008;3:431–44.PubMed
32.
Rivas D, Li W, Akter R, et al. Accelerated features of age-related bone loss in zmpste24 metalloproteinase-deficient mice. J Gerontol A Biol Sci Med Sci. 2009;64:1015–24.PubMedCrossRef
33.
Merideth MA, Gordon LB, Clauss S, et al. Phenotype and course of Hutchinson-Gilford progeria syndrome. N Engl J Med. 2008;358:592–604.PubMedCrossRef
34.
Akter R, Rivas D, Geneau G, et al. Effect of lamin A/C knockdown on osteoblast differentiation and function. J Bone Miner Res. 2009;24:283–93.PubMedCrossRef
35.
Liu LF, Shen WJ, Zhang ZH, et al. Adipocytes decrease Runx2 expression in osteoblastic cells: roles of PPARγ and adiponectin. J Cell Physiol. 2010;225:837–45.PubMedCrossRef
36.
Mackall JC, Student AK, Polakis SE, et al. Induction of lipogenesis during differentiation in a "preadipocyte" cell line. J Biol Chem. 1976;251:6462–4.PubMed
37.
Liu P, Oyajobi BO, Russell RG, et al. Regulation of osteogenic differentiation of human bone marrow stromal cells: interaction between transforming growth factor-beta and 1,25(OH)(2) vitamin D(3) in vitro. Calcif Tissue Int. 1999;65:173–80.PubMedCrossRef
38.
Zhou S, LeBoff MS, Glowacki J. Vitamin D metabolism and action in human bone marrow stromal cells. Endocrinology. 2010;151:14–22.PubMedCrossRef
39.
Geng S, Zhou S, Glowacki J. Age-related decline in osteoblastogenesis and 1alpha-hydroxylase/CYP27B1 in human mesenchymal stem cells: stimulation by parathyroid hormone. Aging Cell. 2011;10:962–71.PubMedCrossRef
40.
Takahashi K, Tsuboyama T, Matsushita M, et al. Modification of strain-specific femoral bone density by bone marrow-derived factors administered neonatally: a study on the spontaneously osteoporotic mouse, SAMP6. Bone Miner. 1994;24:245–55.PubMedCrossRef
41.
Kajkenova O, Lecka-Czernik B, Gubrij I, et al. Increased adipogenesis and myelopoiesis in the bone marrow of SAMP6, a murine model of defective osteoblastogenesis and low turnover osteopenia. J Bone Miner Res. 1997;12:1772–9.PubMedCrossRef
42.
Moerman EJ, Teng K, Lipschitz DA, et al. Aging activates adipogenic and suppresses osteogenic programs in mesenchymal marrow stroma/stem cells: the role of PPAR-γ2 transcription factor and TGF-beta/BMP signaling pathways. Aging Cell. 2004;3:379–89.PubMedCrossRef
43.
Sohal RS, Allen RG. Relationship between metabolic rate, free radicals, differentiation, and aging: a unified theory. Basic Life Sci. 1985;35:75–104.PubMed
44.
• Almeida M, Ambrogini E, Han L, et al. Increased lipid oxidation causes oxidative stress, increased peroxisome proliferator-activated receptor-gamma expression, and diminished pro-osteogenic Wnt signaling in the skeleton. J Biol Chem. 2009;284:27438–48. This study examines how oxidative stresses may be contributing to osteoporosis, which will help address the disease in men and continued bone loss in women long after menopause.PubMedCrossRef
45.
Morse D, Choi AM. Heme oxygenase-1: the “emerging molecule” has arrived. Am J Respir Cell Mol Biol. 2002;27:8–16.PubMedCrossRef
46.
Vanella L, Kim DH, Asprinio D, et al. HO-1 expression increases mesenchymal stem cell-derived osteoblasts but decreases adipocyte lineage. Bone. 2010;46:236–43.PubMedCrossRef
47.
Keane EM, Healy M, O'Moore R, et al. Hypovitaminosis D in the healthy elderly. Br J Clin Pract. 1995;49:301–3.PubMed
48.
Kelly KA, Gimble JM. 1,25-Dihydroxy vitamin D3 inhibits adipocyte differentiation and gene expression in murine bone marrow stromal cell clones and primary cultures. Endocrinology. 1998;139:2622–8.PubMedCrossRef
49.
Duque G, Macoritto M, Kremer R. 1,25(OH)2D3 inhibits bone marrow adipogenesis in senescence accelerated mice (SAM-P/6) by decreasing the expression of peroxisome proliferator-activated receptor gamma 2 (PPARγ2). Exp Gerontol. 2004;39:333–8.PubMedCrossRef
50.
Krum SA, Wend K. Estrogen receptor alpha regulation of bone marrow adipogenesis. Annual meeting of the American Society of Bone and Mineral Research. UCLA, USA; 2012.
51.
Saely CH, Geiger K, Drexel H. Brown vs white adipose tissue: a mini-review. Gerontology. 2012;58:15–23.PubMedCrossRef
52.
• Krings A, Rahman S, Huang S, et al. Bone marrow fat has brown adipose tissue characteristics, which are attenuated with aging and diabetes. Bone. 2012;50:546–52. Although this has not been confirmed in humans, this study demonstrates that bone marrow APs in mice are not homogenous and have characteristics of both white and brown adipose tissue, which may have implications in hematopoiesis.PubMedCrossRef
53.
Guralnik JM, Eisenstaedt RS, Ferrucci L, et al. Prevalence of anemia in persons 65 years and older in the United States: evidence for a high rate of unexplained anemia. Blood. 2004;104:2263–8.PubMedCrossRef
54.
Beghe C, Wilson A, Ershler WB. Prevalence and outcomes of anemia in geriatrics: a systematic review of the literature. Am J Med. 2004;116(Suppl 7A):3S–10S.PubMedCrossRef
55.
56.
Hakim FT, Gress RE. Immunosenescence: deficits in adaptive immunity in the elderly. Tissue Antigens. 2007;70:179–89.PubMedCrossRef
57.
Linton PJ, Dorshkind K. Age-related changes in lymphocyte development and function. Nat Immunol. 2004;5:133–9.PubMedCrossRef
58.
Henry CJ, Marusyk A, DeGregori J. Aging-associated changes in hematopoiesis and leukemogenesis: what's the connection? Aging. 2011;3:643–56.PubMed
59.
Belaid-Choucair Z, Lepelletier Y, Poncin G, et al. Human bone marrow adipocytes block granulopoiesis through neuropilin-1-induced granulocyte colony-stimulating factor inhibition. Stem Cells. 2008;26:1556–64.PubMedCrossRef
60.
Belaid Z, Hubint F, Humblet C, et al. Differential expression of vascular endothelial growth factor and its receptors in hematopoietic and fatty bone marrow: evidence that neuropilin-1 is produced by fat cells. Haematologica. 2005;90:400–1.PubMed
61.
•• Poncin G, Beaulieu A, Humblet C, et al. Characterization of spontaneous bone marrow recovery after sublethal total body irradiation: importance of the osteoblastic/adipocytic balance. PLoS One. 2012;7:e30818. This study suggests that elevated Runx2 expression was important in initiating hematopoietic cell recovery following radiation, while PPARγ expression was suppressed as recovery progressed. Therefore, the lack of OB lineage cells (and surplus of APs) in aging may account, at least in part, for declining hematopoiesis in the elderly.PubMedCrossRef
62.
•• Naveiras O, Nardi V, Wenzel PL, et al. Bone-marrow adipocytes as negative regulators of the haematopoietic microenvironment. Nature. 2009;460:259–63. Here, the investigators found that APs can inhibit hematopoiesis at the level of the HSC, affecting all hematopoietic lineages.PubMedCrossRef
63.
Zhu RJ, Wu MQ, Li ZJ, et al. Hematopoietic recovery following chemotherapy is improved by BADGE-induced inhibition of adipogenesis. Int J Hematol. 2012. Epub ahead of print.
64.
Spangrude GJ, Aihara Y, Weissman IL, et al. The stem cell antigens Sca-1 and Sca-2 subdivide thymic and peripheral T lymphocytes into unique subsets. J Immunol. 1988;141:3697–707.PubMed
65.
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.PubMedCrossRef
66.
•• Nishio M, Yoneshiro T, Nakahara M, et al. Production of functional classical brown adipocytes from human pluripotent stem cells using specific hemopoietin cocktail without gene transfer. Cell Metab. 2012;16:394–406. This study shows for the first time, a direct connection between human BAT and hematopoeisis. Murine bone marrow APs have been shown to have characteristics of BAT which diminishes with aging. If the same is true in humans, this may also be an important factor in hematopoietic decline with aging.PubMedCrossRef
67.
Calvi LM, Adams GB, Weibrecht KW, et al. Osteoblastic cells regulate the haematopoietic stem cell niche. Nature. 2003;425:841–6.PubMedCrossRef
68.
Arai F, Hirao A, Suda T. Regulation of hematopoietic stem cells by the niche. Trends Cardiovasc Med. 2005;15:75–9.PubMedCrossRef
69.
Jung Y, Wang J, Song J, et al. Annexin II expressed by osteoblasts and endothelial cells regulates stem cell adhesion, homing, and engraftment following transplantation. Blood. 2007;110:82–90.PubMedCrossRef
70.
Jung Y, Song J, Shiozawa Y, et al. Hematopoietic stem cells regulate mesenchymal stromal cell induction into osteoblasts thereby participating in the formation of the stem cell niche. Stem Cells. 2008;26:2042–51.PubMedCrossRef
71.
Liao J, Hammerick KE, Challen GA, et al. Investigating the role of hematopoietic stem and progenitor cells in regulating the osteogenic differentiation of mesenchymal stem cells in vitro. J Orthop Res. 2011;29:1544–53.PubMedCrossRef
72.
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.PubMedCrossRef
Metadata
Title
The Changing Balance Between Osteoblastogenesis and Adipogenesis in Aging and its Impact on Hematopoiesis
Authors
Monique Bethel
Brahmananda R. Chitteti
Edward F. Srour
Melissa A. Kacena
Publication date
01-06-2013
Publisher
Current Science Inc.
Published in
Current Osteoporosis Reports / Issue 2/2013
Print ISSN: 1544-1873
Electronic ISSN: 1544-2241
DOI
https://doi.org/10.1007/s11914-013-0135-6

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