Current Osteoporosis Reports

, Volume 16, Issue 2, pp 95–104 | Cite as

Metabolic Coupling Between Bone Marrow Adipose Tissue and Hematopoiesis

  • Russell T. Turner
  • Stephen A. Martin
  • Urszula T. Iwaniec
Bone Marrow and Adipose Tissue (G Duque and B Lecka-Czernik, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Bone Marrow and Adipose Tissue

Abstract

Purpose of Review

Mesenchymal stem cells (MSCs) located in the bone marrow have the capacity to differentiate into multiple cell lineages, including osteoblast and adipocyte. Adipocyte density within marrow is inversely associated with bone mass during aging and in some pathological conditions, contributing to the prevailing view that marrow adipocytes play a largely negative role in bone metabolism. However, a negative association between marrow adipocytes and bone balance is not universal. Although MAT levels appear tightly regulated, establishing the precise physiological significance of MAT has proven elusive. Here, we review recent literature aimed at delineating the function of MAT.

Recent Findings

An important physiological function of MAT may be to provide an expandable/contractible fat depot, which is critical for minimization of energy requirements for sustaining optimal hematopoiesis. Because the energy requirements for storing fat are negligible compared to those required to maintain hematopoiesis, even small reductions in hematopoietic tissue volume to match a reduced requirement for hematopoiesis could represent an important reduction in energy cost. Such a physiological function would require tight coupling between hematopoietic stem cells and MSCs to regulate the balance between MAT and hematopoiesis. Kit-ligand, an important regulator of proliferation, differentiation, and survival of hematopoietic cells, may function as a prototypic factor coupling MAT and hematopoiesis.

Summary

Crosstalk between hematopoietic and mesenchymal cells in the bone marrow may contribute to establishing the balance between MAT levels and hematopoiesis.

Keywords

Adipocyte Osteoblast Hematopoiesis Kit-ligand Bone remodeling 

Notes

Acknowledgements

Grants from the National Institutes of Health (AR060913 and AR066811) and the National Aeronautics and Space Administration (NNX12AL24) supported this work.

Compliance with Ethical Standards

Conflict of Interest

Russell Turner and Urszula Iwaniec report grants from the NIH and NASA during the conduct of this study. Stephen Martin declares no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Morrison SJ, Scadden DT. The bone marrow niche for haematopoietic stem cells. Nature. 2014;505(7483):327–34.  https://doi.org/10.1038/nature12984.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Lichtman MA. The ultrastructure of the hemopoietic environment of the marrow: a review. Exp Hematol. 1981;9(4):391–410.PubMedGoogle Scholar
  3. 3.
    Tavassoli M, Friedenstein A. Hemopoietic stromal microenvironment. Am J Hematol. 1983;15(2):195–203.  https://doi.org/10.1002/ajh.2830150211.CrossRefPubMedGoogle Scholar
  4. 4.
    Allen TD, Dexter TM, Simmons PJ. Marrow biology and stem cells. Immunol Ser. 1990;49:1–38.PubMedGoogle Scholar
  5. 5.
    Beresford JN, Bennett JH, Devlin C, Leboy PS, Owen ME. Evidence for an inverse relationship between the differentiation of adipocytic and osteogenic cells in rat marrow stromal cell cultures. J Cell Sci. 1992;102(Pt 2):341–51.PubMedGoogle Scholar
  6. 6.
    Vaananen HK, Laitala-Leinonen T. Osteoclast lineage and function. Arch Biochem Biophys. 2008;473(2):132–8.  https://doi.org/10.1016/j.abb.2008.03.037.CrossRefPubMedGoogle Scholar
  7. 7.
    • 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. This paper is a must-read for anyone interested in MAT. As a side note - Charles Brenton Huggins was awarded the Nobel Prize for his pioneering work on hormonal regulation of prostate cancer.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Lecka-Czernik B. Marrow fat metabolism is linked to the systemic energy metabolism. Bone. 2012;50(2):534–9.  https://doi.org/10.1016/j.bone.2011.06.032.CrossRefPubMedGoogle Scholar
  9. 9.
    Craft CS, Scheller EL. Evolution of the marrow adipose tissue microenvironment. Calcif Tissue Int. 2017;100(5):461–75.  https://doi.org/10.1007/s00223-016-0168-9.CrossRefPubMedGoogle Scholar
  10. 10.
    Scheller EL, Burr AA, MacDougald OA, Cawthorn WP. Inside out: bone marrow adipose tissue as a source of circulating adiponectin. Adipocyte. 2016;5(3):251–69.  https://doi.org/10.1080/21623945.2016.1149269.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Scheller EL, Cawthorn WP, Burr AA, Horowitz MC, MacDougald OA. Marrow adipose tissue: trimming the fat. Trends Endocrinol Metab. 2016;27(6):392–403.  https://doi.org/10.1016/j.tem.2016.03.016.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Sulston RJ, Cawthorn WP. Bone marrow adipose tissue as an endocrine organ: close to the bone? Horm Mol Biol Clin Invest. 2016;28(1):21–38.  https://doi.org/10.1515/hmbci-2016-0012.Google Scholar
  14. 14.
    Lecka-Czernik B, Stechschulte LA. Bone and fat: a relationship of different shades. Arch Biochem Biophys. 2014;561:124–9.  https://doi.org/10.1016/j.abb.2014.06.010.CrossRefPubMedGoogle Scholar
  15. 15.
    Ghali O, Al Rassy N, Hardouin P, Chauveau C. Increased bone marrow adiposity in a context of energy deficit: the tip of the iceberg? Front Endocrinol. 2016;7:125.  https://doi.org/10.3389/fendo.2016.00125.CrossRefGoogle Scholar
  16. 16.
    Hamrick MW, McGee-Lawrence ME, Frechette DM. Fatty infiltration of skeletal muscle: mechanisms and comparisons with bone marrow adiposity. Front Endocrinol. 2016;7:69.  https://doi.org/10.3389/fendo.2016.00069.CrossRefGoogle Scholar
  17. 17.
    Kim TY, Schafer AL. Diabetes and bone marrow adiposity. Curr Osteoporos Rep. 2016;14(6):337–44.  https://doi.org/10.1007/s11914-016-0336-x.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Pagnotti GM, Styner M. Exercise regulation of marrow adipose tissue. Front Endocrinol. 2016;7:94.  https://doi.org/10.3389/fendo.2016.00094.CrossRefGoogle Scholar
  19. 19.
    Chkourko Gusky H, Diedrich J, MacDougald OA, Podgorski I. Omentum and bone marrow: how adipocyte-rich organs create tumour microenvironments conducive for metastatic progression. Obes Rev : Off J Int Assoc Study Obes. 2016;17(11):1015–29.  https://doi.org/10.1111/obr.12450.CrossRefGoogle Scholar
  20. 20.
    Morris EV, Edwards CM. Bone marrow adipose tissue: a new player in cancer metastasis to bone. Front Endocrinol. 2016;7:90.  https://doi.org/10.3389/fendo.2016.00090.CrossRefGoogle Scholar
  21. 21.
    Justesen J, Stenderup K, Ebbesen EN, Mosekilde L, Steiniche T, Kassem M. Adipocyte tissue volume in bone marrow is increased with aging and in patients with osteoporosis. Biogerontology. 2001;2(3):165–71.  https://doi.org/10.1023/A:1011513223894.CrossRefPubMedGoogle Scholar
  22. 22.
    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 : JMRI. 2012;36(1):225–30.  https://doi.org/10.1002/jmri.23619.CrossRefPubMedGoogle Scholar
  23. 23.
    Tavassoli M. Marrow adipose cells. Histochemical identification of labile and stable components. Arch Pathol Lab Med. 1976;100(1):16–8.PubMedGoogle Scholar
  24. 24.
    Scheller EL, Doucette CR, Learman BS, Cawthorn WP, Khandaker S, Schell B, et al. Region-specific variation in the properties of skeletal adipocytes reveals regulated and constitutive marrow adipose tissues. Nat Commun. 2015;6(1):7808.  https://doi.org/10.1038/ncomms8808.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Li M, Shen Y, Qi H, Wronski TJ. Comparative study of skeletal response to estrogen depletion at red and yellow marrow sites in rats. Anat Rec. 1996;245(3):472–80.  https://doi.org/10.1002/(SICI)1097-0185(199607)245:3<472::AID-AR3>3.0.CO;2-U.CrossRefPubMedGoogle Scholar
  26. 26.
    Menagh PJ, Turner RT, Jump DB, Wong CP, Lowry MB, Yakar S, et al. Growth hormone regulates the balance between bone formation and bone marrow adiposity. J Bone Miner Res : Off J Am Soc Bone Miner Res. 2010;25(4):757–68.  https://doi.org/10.1359/jbmr.091015.Google Scholar
  27. 27.
    Krings A, Rahman S, Huang S, Lu Y, Czernik PJ, Lecka-Czernik B. Bone marrow fat has brown adipose tissue characteristics, which are attenuated with aging and diabetes. Bone. 2012;50(2):546–52.  https://doi.org/10.1016/j.bone.2011.06.016.CrossRefPubMedGoogle Scholar
  28. 28.
    • Iwaniec UT, Philbrick KA, Wong CP, Gordon JL, Kahler-Quesada AM, Olson DA, et al. Room temperature housing results in premature cancellous bone loss in growing female mice: implications for the mouse as a preclinical model for age-related bone loss. Osteoporos Int. 2016;27(10):3091–101.  https://doi.org/10.1007/s00198-016-3634-3. Mice are conventionally housed at room temperature, which is well below thermoneutral range for this species. In this study, sub-thermoneutral housing was shown to increase nonshivering thermogenesis and bone resorption, and decrease MAT, WAT, bone formation and cancellous bone volume fraction. The magnitude of the changes raise concerns regarding potential misinterpretation of results in mice housed at room temperature because sympathetic and sensory signaling, factors known to influence bone metabolism, regulate thermogenesis.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Oguro H, McDonald JG, Zhao Z, Umetani M, Shaul PW, Morrison SJ. 27-Hydroxycholesterol induces hematopoietic stem cell mobilization and extramedullary hematopoiesis during pregnancy. J Clin Invest. 2017;127(9):3392–401.  https://doi.org/10.1172/JCI94027.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Crandall TL, Joyce RA, Boggs DR. Estrogens and hematopoiesis: characterization and studies on the mechanism of neutropenia. J Lab Clin Med. 1980;95(6):857–67.PubMedGoogle Scholar
  31. 31.
    Nilsson SK, Bertoncello I. Age-related changes in extramedullary hematopoiesis in the spleen of normal and perturbed osteopetrotic (op/op) mice. Exp Hematol. 1994;22(4):377–83.PubMedGoogle Scholar
  32. 32.
    Verma S, Rajaratnam JH, Denton J, Hoyland JA, Byers RJ. Adipocytic proportion of bone marrow is inversely related to bone formation in osteoporosis. J Clin Pathol. 2002;55(9):693–8.  https://doi.org/10.1136/jcp.55.9.693.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Cho SW, Yang JY, Her SJ, Choi HJ, Jung JY, Sun HJ, et al. Osteoblast-targeted overexpression of PPARgamma inhibited bone mass gain in male mice and accelerated ovariectomy-induced bone loss in female mice. J Bone Miner Res : Off J Am Soc Bone Miner Res. 2011;26(8):1939–52.  https://doi.org/10.1002/jbmr.366.CrossRefGoogle Scholar
  34. 34.
    Muruganandan S, Sinal CJ. The impact of bone marrow adipocytes on osteoblast and osteoclast differentiation. IUBMB Life. 2014;66(3):147–55.  https://doi.org/10.1002/iub.1254.CrossRefGoogle Scholar
  35. 35.
    Akune T, Ohba S, Kamekura S, Yamaguchi M, Chung UI, Kubota N, et al. PPARgamma insufficiency enhances osteogenesis through osteoblast formation from bone marrow progenitors. J Clin Invest. 2004;113(6):846–55.  https://doi.org/10.1172/JCI19900.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Pei L, Tontonoz P. Fat’s loss is bone’s gain. J Clin Invest. 2004;113(6):805–6.  https://doi.org/10.1172/JCI21311.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Keune JA, Philbrick KA, Branscum AJ, Iwaniec UT, Turner RT. Spaceflight-induced vertebral bone loss in ovariectomized rats is associated with increased bone marrow adiposity and no change in bone formation. NPJ Microgravity. 2016;2(1):16016.  https://doi.org/10.1038/npjmgrav.2016.16.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    • 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. MAT-deficient mice had increased osteoblast-lined bone perimeter but cancellous bone volume fraction was normal. Hindlimb unloading accentuated bone loss in MAT-deficient mice. These findings do not support the concept that suppressing MAT will always have a beneficial effect on bone turnover balance CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Li M, Liang H, Shen Y, Wronski TJ. Parathyroid hormone stimulates cancellous bone formation at skeletal sites regardless of marrow composition in ovariectomized rats. Bone. 1999;24(2):95–100.  https://doi.org/10.1016/S8756-3282(98)00167-7.CrossRefPubMedGoogle Scholar
  40. 40.
    Hamrick MW, Della-Fera MA, Choi YH, Pennington C, Hartzell D, Baile CA. Leptin treatment induces loss of bone marrow adipocytes and increases bone formation in leptin-deficient ob/ob mice. J Bone Miner Res : Off J Am Soc Bone Miner Res. 2005;20(6):994–1001.  https://doi.org/10.1359/JBMR.050103.CrossRefGoogle Scholar
  41. 41.
    Martin RB, Zissimos SL. Relationships between marrow fat and bone turnover in ovariectomized and intact rats. Bone. 1991;12(2):123–31.  https://doi.org/10.1016/8756-3282(91)90011-7.CrossRefPubMedGoogle Scholar
  42. 42.
    Maddalozzo GF, Turner RT, Edwards CH, Howe KS, Widrick JJ, Rosen CJ, et al. Alcohol alters whole body composition, inhibits bone formation, and increases bone marrow adiposity in rats. Osteoporos Int. 2009;20(9):1529–38.  https://doi.org/10.1007/s00198-009-0836-y.CrossRefPubMedGoogle Scholar
  43. 43.
    Wronski TJ, Morey ER. Skeletal abnormalities in rats induced by simulated weightlessness. Metab Bone Dis Relat Res. 1982;4(1):69–75.  https://doi.org/10.1016/0221-8747(82)90011-X.CrossRefPubMedGoogle Scholar
  44. 44.
    • Fan Y, Hanai JI, Le PT, Bi R, Maridas D, DeMambro V, et al. Parathyroid hormone directs bone marrow mesenchymal cell fate. Cell Metab. 2017;25(3):661–72.  https://doi.org/10.1016/j.cmet.2017.01.001. Deletion of PTH/PTHrP receptor in MSCs resulted in decreased bone formation and increased MAT, suggesting that PTH directs MSC differentiation towards the osteoblast lineage. However, it should be noted that TJ Wronski and colleagues showed in a series of studies that high MAT levels do not impair the skeletal response to intermittent PTH. The Wronski lab also showed that PTH is ineffective in restoring bone in a severely osteopenic skeleton, suggesting that this mechanism does not result in de novo (bone formed where there is no bone) bone formation.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Turner RT, Iwaniec UT. Low dose parathyroid hormone maintains normal bone formation in adult male rats during rapid weight loss. Bone. 2011;48(4):726–32.  https://doi.org/10.1016/j.bone.2010.12.034.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Dobnig H, Turner RT. Evidence that intermittent treatment with parathyroid hormone increases bone formation in adult rats by activation of bone lining cells. Endocrinology. 1995;136(8):3632–8.  https://doi.org/10.1210/endo.136.8.7628403.CrossRefPubMedGoogle Scholar
  47. 47.
    Ambati S, Li Q, Rayalam S, Hartzell DL, Della-Fera MA, Hamrick MW, et al. Central leptin versus ghrelin: effects on bone marrow adiposity and gene expression. Endocrine. 2010;37(1):115–23.  https://doi.org/10.1007/s12020-009-9274-z.CrossRefPubMedGoogle Scholar
  48. 48.
    Bartell SM, Rayalam S, Ambati S, Gaddam DR, Hartzell DL, Hamrick M, et al. Central (ICV) leptin injection increases bone formation, bone mineral density, muscle mass, serum IGF-1, and the expression of osteogenic genes in leptin-deficient ob/ob mice. J Bone Miner Res : Off J Am Soc Bone Miner Res. 2011;26(8):1710–20.  https://doi.org/10.1002/jbmr.406.CrossRefGoogle Scholar
  49. 49.
    Hamrick MW, Della Fera MA, Choi YH, Hartzell D, Pennington C, Baile CA. Injections of leptin into rat ventromedial hypothalamus increase adipocyte apoptosis in peripheral fat and in bone marrow. Cell Tissue Res. 2007;327(1):133–41.  https://doi.org/10.1007/s00441-006-0312-3.CrossRefPubMedGoogle Scholar
  50. 50.
    Lindenmaier LB, Philbrick KA, Branscum AJ, Kalra SP, Turner RT, Iwaniec UT. Hypothalamic leptin gene therapy reduces bone marrow adiposity in ob/ob mice fed regular and high-fat diets. Front Endocrinol. 2016;7:110.  https://doi.org/10.3389/fendo.2016.00110.CrossRefGoogle Scholar
  51. 51.
    Philbrick KA, Wong CP, Branscum AJ, Turner RT, Iwaniec UT. Leptin stimulates bone formation in ob/ob mice at doses having minimal impact on energy metabolism. J Endocrinol. 2017;232(3):461–74.  https://doi.org/10.1530/JOE-16-0484.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    • Devlin MJ, Brooks DJ, Conlon C, Vliet M, Louis L, Rosen CJ, et al. Daily leptin blunts marrow fat but does not impact bone mass in calorie-restricted mice. J Endocrinol. 2016;229(3):295–306.  https://doi.org/10.1530/JOE-15-0473. Caloric restriction in growing mice impaired weight gain and bone accrual but increased MAT. Intermittent leptin treatment reduced MAT but had no impact on bone mass. This study adds further evidence that reducing MAT may not be effective as a strategy for increasing bone mass.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Tracy CR. Minimum size of mammalian homeotherms: role of the thermal environment. Science. 1977;198(4321):1034–5.  https://doi.org/10.1126/science.929184.CrossRefPubMedGoogle Scholar
  55. 55.
    Overton JM. Phenotyping small animals as models for the human metabolic syndrome: thermoneutrality matters. Int J Obes. 2010;34(Suppl 2):S53–8.  https://doi.org/10.1038/ijo.2010.240.CrossRefGoogle Scholar
  56. 56.
    Nakada D, Oguro H, Levi BP, Ryan N, Kitano A, Saitoh Y, et al. Oestrogen increases haematopoietic stem-cell self-renewal in females and during pregnancy. Nature. 2014;505(7484):555–8.  https://doi.org/10.1038/nature12932.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Buenzli PR, Sims NA. Quantifying the osteocyte network in the human skeleton. Bone. 2015;75:144–50.  https://doi.org/10.1016/j.bone.2015.02.016.CrossRefPubMedGoogle Scholar
  58. 58.
    Feng ZC, Riopel M, Popell A, Wang R. A survival kit for pancreatic beta cells: stem cell factor and c-Kit receptor tyrosine kinase. Diabetologia. 2015;58(4):654–65.  https://doi.org/10.1007/s00125-015-3504-0.CrossRefPubMedGoogle Scholar
  59. 59.
    Rojas-Sutterlin S, Lecuyer E, Hoang T. Kit and Scl regulation of hematopoietic stem cells. Curr Opin Hematol. 2014;21(4):256–64.  https://doi.org/10.1097/MOH.0000000000000052.CrossRefPubMedGoogle Scholar
  60. 60.
    Ishijima Y, Ohmori S, Ohneda K. Mast cell deficiency results in the accumulation of preadipocytes in adipose tissue in both obese and non-obese mice. FEBS Open Bio. 2013;4(1):18–24.  https://doi.org/10.1016/j.fob.2013.11.004.CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Mansour A, Abou-Ezzi G, Sitnicka E, Jacobsen SE, Wakkach A, Blin-Wakkach C. Osteoclasts promote the formation of hematopoietic stem cell niches in the bone marrow. J Exp Med. 2012;209(3):537–49.  https://doi.org/10.1084/jem.20110994.CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Wilson A, Trumpp A. Bone-marrow haematopoietic-stem-cell niches. Nat Rev Immunol. 2006;6(2):93–106.  https://doi.org/10.1038/nri1779.CrossRefPubMedGoogle Scholar
  63. 63.
    • Mattiucci D, Maurizi G, Izzi V, Cenci L, Ciarlantini M, Mancini S, et al. Bone marrow adipocytes support hematopoietic stem cell survival. J Cell Physiol. 2017;  https://doi.org/10.1002/jcp.26037. It is well known that stromal cells support hematopoiesis in vitro . The results of this study suggest that bone marrow adipocytes (1) are more closely related to bone marrow MSCs than to subcutaneous adipocytes and (2) directly sustain HSC survival.
  64. 64.
    • Zhou BO, Yu H, Yue R, Zhao Z, Rios JJ, Naveiras O, et al. Bone marrow adipocytes promote the regeneration of stem cells and haematopoiesis by secreting SCF. Nat Cell Biol. 2017;19(8):891–903.  https://doi.org/10.1038/ncb3570. c-Kit/Kit ligand (SCF) signaling is essential for hematopoiesis. Kit-ligand is known to be expressed by connective tissue cells, including osteoblasts. This study suggests that bone marrow adipocytes also support hematopoiesis through c-kit signaling.CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Turner RT, Wong CP, Iwaniec UT. Effect of reduced c-kit signaling on bone marrow adiposity. Anat Rec. 2011;294(7):1126–34.  https://doi.org/10.1002/ar.21409.CrossRefGoogle Scholar
  66. 66.
    Iwaniec UT, Turner RT. Failure to generate bone marrow adipocytes does not protect mice from ovariectomy-induced osteopenia. Bone. 2013;53(1):145–53.  https://doi.org/10.1016/j.bone.2012.11.034.CrossRefPubMedGoogle Scholar
  67. 67.
    Hatanaka K, Tanishita H, Ishibashi-Ueda H, Yamamoto A. Hyperlipidemia in mast cell-deficient W/WV mice. Biochim Biophys Acta. 1986;878(3):440–5.  https://doi.org/10.1016/0005-2760(86)90254-7.CrossRefPubMedGoogle Scholar
  68. 68.
    Agostino NM, Chinchilli VM, Lynch CJ, Koszyk-Szewczyk A, Gingrich R, Sivik J, et al. Effect of the tyrosine kinase inhibitors (sunitinib, sorafenib, dasatinib, and imatinib) on blood glucose levels in diabetic and nondiabetic patients in general clinical practice. J Oncol Pharm Pract : Off Publ Int Soc Oncol Pharm Practitioners. 2011;17(3):197–202.  https://doi.org/10.1177/1078155210378913.CrossRefGoogle Scholar
  69. 69.
    Hagerkvist R, Jansson L, Welsh N. Imatinib mesylate improves insulin sensitivity and glucose disposal rates in rats fed a high-fat diet. Clin Sci. 2008;114(1):65–71.  https://doi.org/10.1042/CS20070122.CrossRefPubMedGoogle Scholar
  70. 70.
    Turner RT, Iwaniec UT, Marley K, Sibonga JD. The role of mast cells in parathyroid bone disease. J Bone Miner Res : Off J Am Soc Bone Miner Res. 2010;25(7):1637–49.  https://doi.org/10.1002/jbmr.49.CrossRefGoogle Scholar
  71. 71.
    Hartsock RJ, Smith EB, Petty CS. Normal variations with aging of the amount of hematopoietic tissue in bone marrow from the anterior iliac crest. A study made from 177 cases of sudden death examined by necropsy. Am J Clin Pathol. 1965;43(4):326–31.  https://doi.org/10.1093/ajcp/43.4.326.CrossRefPubMedGoogle Scholar
  72. 72.
    Muschler GF, Nitto H, Boehm CA, Easley KA. Age- and gender-related changes in the cellularity of human bone marrow and the prevalence of osteoblastic progenitors. J Orthop Res : Off Publ Orthop Res Soc. 2001;19(1):117–25.  https://doi.org/10.1016/S0736-0266(00)00010-3.CrossRefGoogle Scholar
  73. 73.
    Huang JS, Mulkern RV, Grinspoon S. Reduced intravertebral bone marrow fat in HIV-infected men. AIDS. 2002;16(9):1265–9.  https://doi.org/10.1097/00002030-200206140-00009.CrossRefPubMedGoogle Scholar
  74. 74.
    Osgood E, Muddassir S, Jaju M, Moser R, Farid F, Mewada N. Starvation marrow—gelatinous transformation of bone marrow. J Community Hosp Intern Med Perspect. 2014;4(4)  https://doi.org/10.3402/jchimp.v4.24811.
  75. 75.
    Saucillo DC, Gerriets VA, Sheng J, Rathmell JC, Maciver NJ. Leptin metabolically licenses T cells for activation to link nutrition and immunity. J Immunol. 2014;192(1):136–44.  https://doi.org/10.4049/jimmunol.1301158.CrossRefPubMedGoogle Scholar
  76. 76.
    Tornvig L, Mosekilde LI, Justesen J, Falk E, Kassem M. Troglitazone treatment increases bone marrow adipose tissue volume but does not affect trabecular bone volume in mice. Calcif Tissue Int. 2001;69(1):46–50.  https://doi.org/10.1007/s002230020018.CrossRefPubMedGoogle Scholar
  77. 77.
    Boyd AL, Reid JC, Salci KR, Aslostovar L, Benoit YD, Shapovalova Z, et al. Acute myeloid leukaemia disrupts endogenous myelo-erythropoiesis by compromising the adipocyte bone marrow niche. Nat Cell Biol. 2017;19(11):1336–47.  https://doi.org/10.1038/ncb3625.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Russell T. Turner
    • 1
    • 2
  • Stephen A. Martin
    • 1
  • Urszula T. Iwaniec
    • 1
    • 2
  1. 1.Skeletal Biology Laboratory, School of Biological and Population Health SciencesOregon State UniversityCorvallisUSA
  2. 2.Center for Healthy Aging ResearchOregon State UniversityCorvallisUSA

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