Top

Current Osteoporosis Reports

Published in:

01-04-2018 | Bone Marrow and Adipose Tissue (G Duque and B Lecka-Czernik, Section Editors)

Marrow Adiposity and Hematopoiesis in Aging and Obesity: Exercise as an Intervention

Authors: Vihitaben S. Patel, M. Ete Chan, Janet Rubin, Clinton T. Rubin

Published in: Current Osteoporosis Reports | Issue 2/2018

Abstract

Purpose of Review

Changes in the bone marrow microenvironment, which accompany aging and obesity, including increased marrow adiposity, can compromise hematopoiesis. Here, we review deleterious shifts in molecular, cellular, and tissue activity and consider the potential of exercise to slow degenerative changes associated with aging and obesity.

Recent Findings

While bone marrow hematopoietic stem cells (HSC) are increased in frequency and myeloid-biased with age, the effect of obesity on HSC proliferation and differentiation remains controversial. HSC from both aged and obese environment have reduced hematopoietic reconstitution capacity following bone marrow transplant. Increased marrow adiposity affects HSC function, causing upregulation of myelopoiesis and downregulation of lymphopoiesis. Exercise, in contrast, can reduce marrow adiposity and restore hematopoiesis.

Summary

The impact of marrow adiposity on hematopoiesis is determined mainly through correlations. Mechanistic studies are needed to determine a causative relationship between marrow adiposity and declines in hematopoiesis, which could aid in developing treatments for conditions that arise from disruptions in the marrow microenvironment.

Travlos GS. Normal structure, function, and histology of the bone marrow. Toxicol Pathol. 2006;34(5):548–65. https://doi.org/10.1080/01926230600939856.CrossRefPubMed

Augello A, De Bari C. The regulation of differentiation in mesenchymal stem cells. Hum Gene Ther. 2010;21(10):1226–38. https://doi.org/10.1089/hum.2010.173.CrossRefPubMed

Luu YK, Capilla E, Rosen CJ, Gilsanz V, Pessin JE, Judex S, et al. Mechanical stimulation of mesenchymal stem cell proliferation and differentiation promotes osteogenesis while preventing dietary-induced obesity. J Bone Miner Res. 2009;24(1):50–61. https://doi.org/10.1359/jbmr.080817.CrossRefPubMed

Alvarez-Viejo M, Menendez-Menendez Y, Blanco-Gelaz MA, Ferrero-Gutierrez A, Fernandez-Rodriguez MA, Gala J, et al. Quantifying mesenchymal stem cells in the mononuclear cell fraction of bone marrow samples obtained for cell therapy. Transplant Proc. 2013;45(1):434–9. https://doi.org/10.1016/j.transproceed.2012.05.091.CrossRefPubMed

•• Patel VS, Chan ME, Pagnotti GM, Frechette DM, Rubin J, Rubin CT. Incorporating refractory period in mechanical stimulation mitigates obesity-induced adipose tissue dysfunction in adult mice. Obesity (Silver Spring). 2017;25(10):1745–53. https://doi.org/10.1002/oby.21958. This study demonstrates that obesity leads to systemic chronic inflammatory state by inducing increased infiltration of immune cells in the adipose tissue, which is restored via whole-body vibration. In addition, this study emphasizes that in adults, whole-body vibration treatment is only effective when it is separated with a rest period. CrossRef

Wang Y, Yu X, Chen E, Li L. Liver-derived human mesenchymal stem cells: a novel therapeutic source for liver diseases. Stem Cell Res Ther. 2016;7(1):71. https://doi.org/10.1186/s13287-016-0330-3.CrossRefPubMedPubMedCentral

Seeberger KL, Dufour JM, Shapiro AM, Lakey JR, Rajotte RV, Korbutt GS. Expansion of mesenchymal stem cells from human pancreatic ductal epithelium. Lab Investig. 2006;86(2):141–53. https://doi.org/10.1038/labinvest.3700377.CrossRefPubMed

Yin L, Zhu Y, Yang J, Ni Y, Zhou Z, Chen Y, et al. Adipose tissue-derived mesenchymal stem cells differentiated into hepatocyte-like cells in vivo and in vitro. Mol Med Rep. 2015;11(3):1722–32. https://doi.org/10.3892/mmr.2014.2935.CrossRefPubMed

Rubin CT, Capilla E, Luu YK, Busa B, Crawford H, Nolan DJ, et al. Adipogenesis is inhibited by brief, daily exposure to high-frequency, extremely low-magnitude mechanical signals. Proc Natl Acad Sci U S A. 2007;104(45):17879–84. https://doi.org/10.1073/pnas.0708467104.CrossRefPubMedPubMedCentral

10.

da Silva SV, Renovato-Martins M, Ribeiro-Pereira C, Citelli M, Barja-Fidalgo C. Obesity modifies bone marrow microenvironment and directs bone marrow mesenchymal cells to adipogenesis. Obesity (Silver Spring). 2016;24(12):2522–32. https://doi.org/10.1002/oby.21660.CrossRef

11.

Chan ME, Adler BJ, Green DE, Rubin CT. Bone structure and B-cell populations, crippled by obesity, are partially rescued by brief daily exposure to low-magnitude mechanical signals. FASEB J. 2012;26(12):4855–63. https://doi.org/10.1096/fj.12-209841.CrossRefPubMedPubMedCentral

12.

•• Adler BJ, Green DE, Pagnotti GM, Chan ME, Rubin CT. High fat diet rapidly suppresses B lymphopoiesis by disrupting the supportive capacity of the bone marrow niche. PLoS One. 2014;9(3):e90639. https://doi.org/10.1371/journal.pone.0090639. This paper demonstrates that high-fat diet leads to increase in marrow adiposity, paralleled by reduced B lymphopoiesis and increased myelopoiesis. CrossRefPubMedPubMedCentral

13.

Orkin SH, Zon LI. Hematopoiesis: an evolving paradigm for stem cell biology. Cell. 2008;132(4):631–44. https://doi.org/10.1016/j.cell.2008.01.025.CrossRefPubMedPubMedCentral

14.

Notta F, Doulatov S, Laurenti E, Poeppl A, Jurisica I, Dick JE. Isolation of single human hematopoietic stem cells capable of long-term multilineage engraftment. Science. 2011;333(6039):218–21. https://doi.org/10.1126/science.1201219.CrossRefPubMed

15.

Tesio M, Tang Y, Mudder K, Saini M, von Paleske L, Macintyre E, et al. Hematopoietic stem cell quiescence and function are controlled by the CYLD-TRAF2-p38MAPK pathway. J Exp Med. 2015;212(4):525–38. https://doi.org/10.1084/jem.20141438.CrossRefPubMedPubMedCentral

16.

Challen GA, Boles N, Lin KK, Goodell MA. Mouse hematopoietic stem cell identification and analysis. Cytometry A. 2009;75(1):14–24. https://doi.org/10.1002/cyto.a.20674.CrossRefPubMedPubMedCentral

17.

Pang WW, Price EA, Sahoo D, Beerman I, Maloney WJ, Rossi DJ, et al. Human bone marrow hematopoietic stem cells are increased in frequency and myeloid-biased with age. Proc Natl Acad Sci U S A. 2011;108(50):20012–7. https://doi.org/10.1073/pnas.1116110108.CrossRefPubMedPubMedCentral

18.

Franco RS. Measurement of red cell lifespan and aging. Transfus Med Hemother. 2012;39(5):302–7. https://doi.org/10.1159/000342232.CrossRefPubMedPubMedCentral

19.

Dzierzak E, Philipsen S. Erythropoiesis: development and differentiation. Cold Spring Harb Perspect Med. 2013;3(4):a011601. https://doi.org/10.1101/cshperspect.a011601.CrossRefPubMedPubMedCentral

20.

Cohen JA, Leeksma CH. Determination of the life span of human blood platelets using labelled diisopropylfluorophosphonate. J Clin Investig. 1956;35(9):964–9. https://doi.org/10.1172/jci103356.CrossRefPubMedPubMedCentral

21.

Thon JN, Italiano JE. Platelet formation. Semin Hematol. 2010;47(3):220–6. https://doi.org/10.1053/j.seminhematol.2010.03.005.CrossRefPubMedPubMedCentral

22.

Sprent J, Tough DF. Lymphocyte life-span and memory. Science. 1994;265(5177):1395–400.CrossRefPubMed

23.

Pillay J, den Braber I, Vrisekoop N, Kwast LM, de Boer RJ, Borghans JA, et al. In vivo labeling with 2H2O reveals a human neutrophil lifespan of 5.4 days. Blood. 2010;116(4):625–7. https://doi.org/10.1182/blood-2010-01-259028.CrossRefPubMed

24.

Summers C, Rankin SM, Condliffe AM, Singh N, Peters AM, Chilvers ER. Neutrophil kinetics in health and disease. Trends Immunol. 2010;31(8):318–24. https://doi.org/10.1016/j.it.2010.05.006.CrossRefPubMedPubMedCentral

25.

Park YM, Bochner BS. Eosinophil survival and apoptosis in health and disease. Allergy Asthma Immunol Res. 2010;2(2):87–101. https://doi.org/10.4168/aair.2010.2.2.87.CrossRefPubMedPubMedCentral

26.

Min B, Brown MA, Legros G. Understanding the roles of basophils: breaking dawn. Immunology. 2012;135(3):192–7. https://doi.org/10.1111/j.1365-2567.2011.03530.x.CrossRefPubMedPubMedCentral

27.

Janssen WJ, Bratton DL, Jakubzick CV, Henson PM. Myeloid cell turnover and clearance. Microbiol Spectr. 2016;4(6). https://doi.org/10.1128/microbiolspec.MCHD-0005-2015.

28.

Velten L, Haas SF, Raffel S, Blaszkiewicz S, Islam S, Hennig BP, et al. Human haematopoietic stem cell lineage commitment is a continuous process. Nat Cell Biol. 2017;19(4):271–81. https://doi.org/10.1038/ncb3493.CrossRefPubMedPubMedCentral

29.

Majumdar MK, Thiede MA, Haynesworth SE, Bruder SP, Gerson SL. Human marrow-derived mesenchymal stem cells (MSCs) express hematopoietic cytokines and support long-term hematopoiesis when differentiated toward stromal and osteogenic lineages. J Hematother Stem Cell Res. 2000;9(6):841–8. https://doi.org/10.1089/152581600750062264.CrossRefPubMed

30.

Mishima S, Nagai A, Abdullah S, Matsuda C, Taketani T, Kumakura S, et al. Effective ex vivo expansion of hematopoietic stem cells using osteoblast-differentiated mesenchymal stem cells is CXCL12 dependent. Eur J Haematol. 2010;84(6):538–46. https://doi.org/10.1111/j.1600-0609.2010.01419.x.CrossRefPubMed

31.

Carrancio S, Blanco B, Romo C, Muntion S, Lopez-Holgado N, Blanco JF, et al. Bone marrow mesenchymal stem cells for improving hematopoietic function: an in vitro and in vivo model. Part 2: effect on bone marrow microenvironment. PLoS One. 2011;6(10):e26241. https://doi.org/10.1371/journal.pone.0026241.CrossRefPubMedPubMedCentral

32.

Bartholomew A, Sturgeon C, Siatskas M, Ferrer K, McIntosh K, Patil S, et al. Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol. 2002;30(1):42–8.CrossRefPubMed

33.

Nemeth K, Leelahavanichkul A, Yuen PS, Mayer B, Parmelee A, Doi K, et al. Bone marrow stromal cells attenuate sepsis via prostaglandin E(2)-dependent reprogramming of host macrophages to increase their interleukin-10 production. Nat Med. 2009;15(1):42–9. https://doi.org/10.1038/nm.1905.CrossRefPubMed

34.

Roddy GW, Oh JY, Lee RH, Bartosh TJ, Ylostalo J, Coble K, et al. Action at a distance: systemically administered adult stem/progenitor cells (MSCs) reduce inflammatory damage to the cornea without engraftment and primarily by secretion of TNF-alpha stimulated gene/protein 6. Stem Cells. 2011;29(10):1572–9. https://doi.org/10.1002/stem.708.CrossRefPubMed

35.

Taichman RS, Emerson SG. The role of osteoblasts in the hematopoietic microenvironment. Stem Cells. 1998;16(1):7–15. https://doi.org/10.1002/stem.160007.CrossRefPubMed

36.

Takahashi N, Udagawa N, Akatsu T, Tanaka H, Shionome M, Suda T. Role of colony-stimulating factors in osteoclast development. J Bone Miner Res. 1991;6(9):977–85. https://doi.org/10.1002/jbmr.5650060912.CrossRefPubMed

37.

Marks SC Jr, Mackay CA, Jackson ME, Larson EK, Cielinski MJ, Stanley ER, et al. The skeletal effects of colony-stimulating factor-1 in toothless (osteopetrotic) rats: persistent metaphyseal sclerosis and the failure to restore subepiphyseal osteoclasts. Bone. 1993;14(4):675–80.CrossRefPubMed

38.

Sanchez-Fernandez MA, Gallois A, Riedl T, Jurdic P, Hoflack B. Osteoclasts control osteoblast chemotaxis via PDGF-BB/PDGF receptor beta signaling. PLoS One. 2008;3(10):e3537. https://doi.org/10.1371/journal.pone.0003537.CrossRefPubMedPubMedCentral

39.

Bonewald LF. The amazing osteocyte. J Bone Miner Res. 2011;26(2):229–38. https://doi.org/10.1002/jbmr.320.CrossRefPubMed

40.

Fulzele K, Krause DS, Panaroni C, Saini V, Barry KJ, Liu X, et al. Myelopoiesis is regulated by osteocytes through Gsα-dependent signaling. Blood. 2013;121(6):930–9. https://doi.org/10.1182/blood-2012-06-437160.CrossRefPubMedPubMedCentral

41.

Yoneshiro T, Aita S, Matsushita M, Okamatsu-Ogura Y, Kameya T, Kawai Y, et al. Age-related decrease in cold-activated brown adipose tissue and accumulation of body fat in healthy humans. Obesity (Silver Spring). 2011;19(9):1755–60. https://doi.org/10.1038/oby.2011.125.CrossRef

42.

Trayhurn P, Beattie JH. Physiological role of adipose tissue: white adipose tissue as an endocrine and secretory organ. Proc Nutr Soc. 2001;60(3):329–39.CrossRefPubMed

43.

Spalding KL, Arner E, Westermark PO, Bernard S, Buchholz BA, Bergmann O, et al. Dynamics of fat cell turnover in humans. Nature. 2008;453(7196):783–7. https://doi.org/10.1038/nature06902.CrossRefPubMed

44.

Meunier P, Aaron J, Edouard C, Vignon G. Osteoporosis and the replacement of cell populations of the marrow by adipose tissue. A quantitative study of 84 iliac bone biopsies. Clin Orthop Relat Res. 1971;80:147–54.CrossRefPubMed

45.

Moore SG, Dawson KL. Red and yellow marrow in the femur: age-related changes in appearance at MR imaging. Radiology. 1990;175(1):219–23. https://doi.org/10.1148/radiology.175.1.2315484.CrossRefPubMed

46.

Scheller EL, Rosen CJ. What’s the matter with MAT? Marrow adipose tissue, metabolism, and skeletal health. Ann N Y Acad Sci. 2014;1311:14–30. https://doi.org/10.1111/nyas.12327.CrossRefPubMedPubMedCentral

47.

Huggins C, Blocksom BH. Changes in outlying bone marrow accompanying a local increase of temperature within physiological limits. J Exp Med. 1936;64(2):253–74.CrossRefPubMedPubMedCentral

48.

Naveiras O, Nardi V, Wenzel PL, Hauschka PV, Fahey F, Daley GQ. Bone-marrow adipocytes as negative regulators of the haematopoietic microenvironment. Nature. 2009;460(7252):259–63. https://doi.org/10.1038/nature08099.CrossRefPubMedPubMedCentral

49.

Scheller EL, Doucette CR, Learman BS, Cawthorn WP, Khandaker S, Schell B, et al. Corrigendum: region-specific variation in the properties of skeletal adipocytes reveals regulated and constitutive marrow adipose tissues. Nat Commun. 2016;7:13775. https://doi.org/10.1038/ncomms13775.CrossRefPubMedPubMedCentral

50.

Lihn AS, Pedersen SB, Richelsen B. Adiponectin: action, regulation and association to insulin sensitivity. Obes Rev. 2005;6(1):13–21. https://doi.org/10.1111/j.1467-789X.2005.00159.x.CrossRefPubMed

51.

Cawthorn WP, Scheller EL, Learman BS, Parlee SD, Simon BR, Mori H, et al. Bone marrow adipose tissue is an endocrine organ that contributes to increased circulating adiponectin during caloric restriction. Cell Metab. 2014;20(2):368–75. https://doi.org/10.1016/j.cmet.2014.06.003.CrossRefPubMedPubMedCentral

52.

Suchacki KJ, Cawthorn WP, Rosen CJ. Bone marrow adipose tissue: formation, function and regulation. Curr Opin Pharmacol. 2016;28:50–6. https://doi.org/10.1016/j.coph.2016.03.001.CrossRefPubMedPubMedCentral

53.

Keune JA, Wong CP, Branscum AJ, Iwaniec UT, Turner RT. Bone marrow adipose tissue deficiency increases disuse-induced bone loss in male mice. Sci Rep. 2017;7:46325. https://doi.org/10.1038/srep46325.CrossRefPubMedPubMedCentral

54.

Ogawa T, Kitagawa M, Hirokawa K. Age-related changes of human bone marrow: a histometric estimation of proliferative cells, apoptotic cells, T cells, B cells and macrophages. Mech Ageing Dev. 2000;117(1–3):57–68.CrossRefPubMed

55.

Pearce DJ, Anjos-Afonso F, Ridler CM, Eddaoudi A, Bonnet D. Age-dependent increase in side population distribution within hematopoiesis: implications for our understanding of the mechanism of aging. Stem Cells. 2007;25(4):828–35. https://doi.org/10.1634/stemcells.2006-0405.CrossRefPubMed

56.

Yahata T, Takanashi T, Muguruma Y, Ibrahim AA, Matsuzawa H, Uno T, et al. Accumulation of oxidative DNA damage restricts the self-renewal capacity of human hematopoietic stem cells. Blood. 2011;118(11):2941–50. https://doi.org/10.1182/blood-2011-01-330050.CrossRefPubMed

57.

Kuranda K, Vargaftig J, de la Rochere P, Dosquet C, Charron D, Bardin F, et al. Age-related changes in human hematopoietic stem/progenitor cells. Aging Cell. 2011;10(3):542–6. https://doi.org/10.1111/j.1474-9726.2011.00675.x.CrossRefPubMed

58.

Ambrosi TH, Scialdone A, Graja A, Gohlke S, Jank AM, Bocian C, et al. Adipocyte accumulation in the bone marrow during obesity and aging impairs stem cell-based hematopoietic and bone regeneration. Cell Stem Cell. 2017;20(6):771–84.e6. https://doi.org/10.1016/j.stem.2017.02.009.CrossRefPubMedPubMedCentral

59.

Griffith JF, Yeung DK, Ma HT, Leung JC, Kwok TC, Leung PC. Bone marrow fat content in the elderly: a reversal of sex difference seen in younger subjects. J Magn Reson Imaging. 2012;36(1):225–30. https://doi.org/10.1002/jmri.23619.CrossRefPubMed

60.

Tuljapurkar SR, McGuire TR, Brusnahan SK, Jackson JD, Garvin KL, Kessinger MA, et al. Changes in human bone marrow fat content associated with changes in hematopoietic stem cell numbers and cytokine levels with aging. J Anat. 2011;219(5):574–81. https://doi.org/10.1111/j.1469-7580.2011.01423.x.CrossRefPubMedPubMedCentral

61.

Reinisch A, Etchart N, Thomas D, Hofmann NA, Fruehwirth M, Sinha S, et al. Epigenetic and in vivo comparison of diverse MSC sources reveals an endochondral signature for human hematopoietic niche formation. Blood. 2015;125(2):249–60. https://doi.org/10.1182/blood-2014-04-572255.CrossRefPubMedPubMedCentral

62.

Trottier MD, Naaz A, Li Y, Fraker PJ. Enhancement of hematopoiesis and lymphopoiesis in diet-induced obese mice. Proc Natl Acad Sci U S A. 2012;109(20):7622–9. https://doi.org/10.1073/pnas.1205129109.CrossRefPubMedPubMedCentral

63.

do Carmo LS, Rogero MM, Paredes-Gamero EJ, Nogueira-Pedro A, Xavier JG, Cortez M, et al. A high-fat diet increases interleukin-3 and granulocyte colony-stimulating factor production by bone marrow cells and triggers bone marrow hyperplasia and neutrophilia in Wistar rats. Exp Biol Med (Maywood). 2013;238(4):375–84. https://doi.org/10.1177/1535370213477976.CrossRef

64.

van den Berg SM, Seijkens TT, Kusters PJ, Beckers L, den Toom M, Smeets E, et al. Diet-induced obesity in mice diminishes hematopoietic stem and progenitor cells in the bone marrow. FASEB J. 2016;30(5):1779–88. https://doi.org/10.1096/fj.201500175.CrossRefPubMed

65.

Singer K, DelProposto J, Morris DL, Zamarron B, Mergian T, Maley N, et al. Diet-induced obesity promotes myelopoiesis in hematopoietic stem cells. Mol Metab. 2014;3(6):664–75. https://doi.org/10.1016/j.molmet.2014.06.005.CrossRefPubMedPubMedCentral

66.

Takahashi K, Mizuarai S, Araki H, Mashiko S, Ishihara A, Kanatani A, et al. Adiposity elevates plasma MCP-1 levels leading to the increased CD11b-positive monocytes in mice. J Biol Chem. 2003;278(47):46654–60. https://doi.org/10.1074/jbc.M309895200.CrossRefPubMed

67.

Nanji AA, Freeman JB. Relationship between body weight and total leukocyte count in morbid obesity. Am J Clin Pathol. 1985;84(3):346–7.CrossRefPubMed

68.

Womack J, Tien PC, Feldman J, Shin JH, Fennie K, Anastos K, et al. Obesity and immune cell counts in women. Metabolism. 2007;56(7):998–1004. https://doi.org/10.1016/j.metabol.2007.03.008.CrossRefPubMedPubMedCentral

69.

Nteeba J, Ortinau LC, Perfield JW 2nd, Keating AF. Diet-induced obesity alters immune cell infiltration and expression of inflammatory cytokine genes in mouse ovarian and peri-ovarian adipose depot tissues. Mol Reprod Dev. 2013;80(11):948–58. https://doi.org/10.1002/mrd.22231.CrossRefPubMed

70.

Caer C, Rouault C, Le Roy T, Poitou C, Aron-Wisnewsky J, Torcivia A, et al. Immune cell-derived cytokines contribute to obesity-related inflammation, fibrogenesis and metabolic deregulation in human adipose tissue. Sci Rep. 2017;7(1):3000. https://doi.org/10.1038/s41598-017-02660-w.CrossRefPubMedPubMedCentral

71.

Doucette CR, Horowitz MC, Berry R, MacDougald OA, Anunciado-Koza R, Koza RA, et al. A high fat diet increases bone marrow adipose tissue (MAT) but does not Alter trabecular or cortical bone mass in C57BL/6J mice. J Cell Physiol. 2015;230(9):2032–7. https://doi.org/10.1002/jcp.24954.CrossRefPubMedPubMedCentral

72.

Scheller EL, Khoury B, Moller KL, Wee NK, Khandaker S, Kozloff KM, et al. Changes in skeletal integrity and marrow adiposity during high-fat diet and after weight loss. Front Endocrinol (Lausanne). 2016;7:102. https://doi.org/10.3389/fendo.2016.00102.

73.

•• Styner M, Thompson WR, Galior K, Uzer G, Wu X, Kadari S, et al. Bone marrow fat accumulation accelerated by high fat diet is suppressed by exercise. Bone. 2014;64:39–46. https://doi.org/10.1016/j.bone.2014.03.044. This paper demonstrates that high-fat diet leads to increased marrow adiposity, which gets suppressed by exercise. CrossRefPubMedPubMedCentral

74.

Bredella MA, Torriani M, Ghomi RH, Thomas BJ, Brick DJ, Gerweck AV, et al. Vertebral bone marrow fat is positively associated with visceral fat and inversely associated with IGF-1 in obese women. Obesity (Silver Spring). 2011;19(1):49–53. https://doi.org/10.1038/oby.2010.106.CrossRef

75.

Caselli A, Olson TS, Otsuru S, Chen X, Hofmann TJ, Nah HD, et al. IGF-1-mediated osteoblastic niche expansion enhances long-term hematopoietic stem cell engraftment after murine bone marrow transplantation. Stem Cells. 2013;31(10):2193–204. https://doi.org/10.1002/stem.1463.CrossRefPubMed

76.

Zhou D, Deoliveira D, Kang Y, Choi SS, Li Z, Chao NJ, et al. Insulin-like growth factor 1 mitigates hematopoietic toxicity after lethal total body irradiation. Int J Radiat Oncol Biol Phys. 2013;85(4):1141–8. https://doi.org/10.1016/j.ijrobp.2012.08.014.CrossRefPubMed

77.

Liang X, Su YP, Kong PY, Zeng DF, Chen XH, Peng XG, et al. Human bone marrow mesenchymal stem cells expressing SDF-1 promote hematopoietic stem cell function of human mobilised peripheral blood CD34+ cells in vivo and in vitro. Int J Radiat Biol. 2010;86(3):230–7. https://doi.org/10.3109/09553000903422555.CrossRefPubMed

78.

Lapidot T, Kollet O. The essential roles of the chemokine SDF-1 and its receptor CXCR4 in human stem cell homing and repopulation of transplanted immune-deficient NOD/SCID and NOD/SCID/B2m(null) mice. Leukemia. 2002;16(10):1992–2003. https://doi.org/10.1038/sj.leu.2402684.CrossRefPubMed

79.

Takeshita S, Fumoto T, Naoe Y, Ikeda K. Age-related marrow adipogenesis is linked to increased expression of RANKL. J Biol Chem. 2014;289(24):16699–710. https://doi.org/10.1074/jbc.M114.547919.CrossRefPubMedPubMedCentral

80.

Holt V, Caplan AI, Haynesworth SE. Identification of a subpopulation of marrow MSC-derived medullary adipocytes that express osteoclast-regulating molecules: marrow adipocytes express osteoclast mediators. PLoS One. 2014;9(10):e108920. https://doi.org/10.1371/journal.pone.0108920.CrossRefPubMedPubMedCentral

81.

• Kennedy DE, Knight KL. Inhibition of B lymphopoiesis by adipocytes and IL-1-producing myeloid-derived suppressor cells. J Immunol. 2015;195(6):2666–74. https://doi.org/10.4049/jimmunol.1500957. This study demonstrates that MAT-induced depletion in B lymphopoiesis is mediated by secretion of IL-1. CrossRefPubMedPubMedCentral

82.

• Huang JY, Zhou QL, Huang CH, Song Y, Sharma AG, Liao Z, et al. Neutrophil elastase regulates emergency myelopoiesis preceding systemic inflammation in diet-induced obesity. J Biol Chem. 2017;292(12):4770–6. https://doi.org/10.1074/jbc.C116.758748. This study demonstrates that obesity-induced myeloid bias is mediated via secretion of neutrophil elastase. CrossRefPubMed

83.

Walji TA, Turecamo SE, Sanchez AC, Anthony BA, Abou-Ezzi G, Scheller EL, et al. Marrow adipose tissue expansion coincides with insulin resistance in MAGP1-deficient mice. Front Endocrinol (Lausanne). 2016;7:87. https://doi.org/10.3389/fendo.2016.00087.PubMedCentral

84.

Fairfield H, Falank C, Harris E, Demambro V, McDonald M, Pettitt JA, et al. The skeletal cell-derived molecule sclerostin drives bone marrow adipogenesis. J Cell Physiol. 2018;233(2):1156–67. https://doi.org/10.1002/jcp.25976.CrossRefPubMed

85.

Ma YH, Schwartz AV, Sigurdsson S, Hue TF, Lang TF, Harris TB, et al. Circulating sclerostin associated with vertebral bone marrow fat in older men but not women. J Clin Endocrinol Metab. 2014;99(12):E2584–90. https://doi.org/10.1210/jc.2013-4493.CrossRefPubMedPubMedCentral

86.

Kohli SS, Kohli VS. Role of RANKL-RANK/osteoprotegerin molecular complex in bone remodeling and its immunopathologic implications. Indian J Endocrinol Metab. 2011;15(3):175–81. https://doi.org/10.4103/2230-8210.83401.CrossRefPubMedPubMedCentral

87.

• Styner M, Pagnotti GM, McGrath C, Wu X, Sen B, Uzer G, et al. Exercise decreases marrow adipose tissue through ß-oxidation in obese running mice. J Bone Miner Res. 2017; https://doi.org/10.1002/jbmr.3159. This study demonstrates that reduction in high-fat diet-induced accumulation in marrow adiposity during exercise is mediated via basal lyposis and β-oxidation, which is partially mediated by perilipin 3.

88.

Shen W, Chen J, Gantz M, Punyanitya M, Heymsfield SB, Gallagher D, et al. MRI-measured pelvic bone marrow adipose tissue is inversely related to DXA-measured bone mineral in younger and older adults. Eur J Clin Nutr. 2012;66(9):983–8. https://doi.org/10.1038/ejcn.2012.35.CrossRefPubMedPubMedCentral

89.

Styner M, Pagnotti GM, McGrath C, Wu X, Sen B, Uzer G, et al. Exercise decreases marrow adipose tissue through ß-oxidation in obese running mice. J Bone Miner Res. 2017;32:1692–702. https://doi.org/10.1002/jbmr.3159.CrossRefPubMedPubMedCentral

90.

Rantalainen T, Nikander R, Heinonen A, Cervinka T, Sievanen H, Daly RM. Differential effects of exercise on tibial shaft marrow density in young female athletes. J Clin Endocrinol Metab. 2013;98(5):2037–44. https://doi.org/10.1210/jc.2012-3748.CrossRefPubMed

91.

Covington JD, Noland RC, Hebert RC, Masinter BS, Smith SR, Rustan AC, et al. Perilipin 3 differentially regulates skeletal muscle lipid oxidation in active, sedentary, and type 2 diabetic males. J Clin Endocrinol Metab. 2015;100(10):3683–92. https://doi.org/10.1210/jc.2014-4125.CrossRefPubMedPubMedCentral

92.

Patel S, Yang W, Kozusko K, Saudek V, Savage DB. Perilipins 2 and 3 lack a carboxy-terminal domain present in perilipin 1 involved in sequestering ABHD5 and suppressing basal lipolysis. Proc Natl Acad Sci U S A. 2014;111(25):9163–8. https://doi.org/10.1073/pnas.1318791111.CrossRefPubMedPubMedCentral

93.

Trudel G, Coletta E, Cameron I, Belavy DL, Lecompte M, Armbrecht G, et al. Resistive exercises, with or without whole body vibration, prevent vertebral marrow fat accumulation during 60 days of head-down tilt bed rest in men. J Appl Physiol. 2012;112(11):1824–31. https://doi.org/10.1152/japplphysiol.00029.2012.CrossRefPubMed

94.

Krishnamoorthy D, Frechette DM, Adler BJ, Green DE, Chan ME, Rubin CT. Marrow adipogenesis and bone loss that parallels estrogen deficiency is slowed by low-intensity mechanical signals. Osteoporos Int. 2016;27(2):747–56. https://doi.org/10.1007/s00198-015-3289-5.CrossRefPubMed

95.

Baker JM, De Lisio M, Parise G. Endurance exercise training promotes medullary hematopoiesis. FASEB J. 2011;25(12):4348–57. https://doi.org/10.1096/fj.11-189043.CrossRefPubMed

96.

De Lisio M, Parise G. Characterization of the effects of exercise training on hematopoietic stem cell quantity and function. J Appl Physiol. 2012;113(10):1576–84. https://doi.org/10.1152/japplphysiol.00717.2012.CrossRefPubMedPubMedCentral

97.

Bonsignore MR, Morici G, Santoro A, Pagano M, Cascio L, Bonanno A, et al. Circulating hematopoietic progenitor cells in runners. J Appl Physiol. 2002;93(5):1691–7. https://doi.org/10.1152/japplphysiol.00376.2002.CrossRefPubMed

98.

Kim HL, Cho HY, Park IY, Choi JM, Kim M, Jang HJ, et al. The positive association between peripheral blood cell counts and bone mineral density in postmenopausal women. Yonsei Med J. 2011;52(5):739–45. https://doi.org/10.3349/ymj.2011.52.5.739.CrossRefPubMedPubMedCentral

99.

Klein-Nulend J, Sterck JG, Semeins CM, Lips P, Joldersma M, Baart JA, et al. Donor age and mechanosensitivity of human bone cells. Osteoporos Int. 2002;13(2):137–46. https://doi.org/10.1007/s001980200005.CrossRefPubMed

100.

Robling AG, Burr DB, Turner CH. Recovery periods restore mechanosensitivity to dynamically loaded bone. J Exp Biol. 2001;204(Pt 19):3389–99.PubMed

101.

Sen B, Xie Z, Case N, Styner M, Rubin CT, Rubin J. Mechanical signal influence on mesenchymal stem cell fate is enhanced by incorporation of refractory periods into the loading regimen. J Biomech. 2011;44(4):593–9. https://doi.org/10.1016/j.jbiomech.2010.11.022.CrossRefPubMed

Title: Marrow Adiposity and Hematopoiesis in Aging and Obesity: Exercise as an Intervention
Authors: Vihitaben S. Patel
M. Ete Chan
Janet Rubin
Clinton T. Rubin
Publication date: 01-04-2018
Publisher: Springer US
Published in: Current Osteoporosis Reports / Issue 2/2018
Print ISSN: 1544-1873
Electronic ISSN: 1544-2241
DOI: https://doi.org/10.1007/s11914-018-0424-1

At a glance: The STEP trials

Springer Medicine

Marrow Adiposity and Hematopoiesis in Aging and Obesity: Exercise as an Intervention

Abstract

Purpose of Review

Recent Findings

Summary

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose of Review

Recent Findings

Summary

Please log in to get access to this content

Other articles of this Issue 2/2018

Transcriptional Mechanisms of Secondary Fracture Healing

Progress of Regenerative Therapy in Orthopedics

Good, Bad, or Ugly: the Biological Roles of Bone Marrow Fat

Screening Gene Knockout Mice for Variation in Bone Mass: Analysis by μCT and Histomorphometry

The Role of the Immune Cells in Fracture Healing

Metabolic Coupling Between Bone Marrow Adipose Tissue and Hematopoiesis