Skip to main content
SpringerLink
Log in

Molecular Differences Between Subtypes of Bone Marrow Adipocytes

  • Molecular Biology of Bone Marrow Fat Adiposity (B van der Eerden, Section Editor)
  • Published:
Current Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Bone marrow adipocytes (BMAs) have distinct molecular properties and physiologic responses depending on their location within the skeleton.

Recent Findings

This concept was introduced in the 1970s and validated more recently in the contexts of cold exposure, sympathetic tone, hematopoiesis, diabetes, lactation, fasting, and caloric restriction.

Summary

In this brief review, we discuss the concept of regulated vs constitutive BMAs, explore their evolutionary and microenvironmental origins, define the site-specific molecular features of BMAs, and discuss the translational implications of the dual bone marrow adipose tissue hypothesis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

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

  1. •• 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(6):7808. Defined regulated and constitutive bone marrow adipocytes.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Bathija A, Davis S, Trubowitz S. Marrow adipose tissue: response to erythropoiesis. Am J Hematol. 1978;5(4):315–21. https://doi.org/10.1002/ajh.2830050406.

    Article  CAS  PubMed  Google Scholar 

  3. • Scheller EL, Khandaker S, Learman BS, Cawthorn WP, Anderson LM, Pham HA, et al. Bone marrow adipocytes resist lipolysis and remodeling in response to β-adrenergic stimulation. Bone. 2018; https://doi.org/10.1016/j.bone.2018.01.016. Details molecular mechanisms underlying reduced responses of rBMAs and cBMAs to fasting and adrenergic cues.

  4. Tavassoli M, Maniatis A, Crosby WH. Induction of sustained hemopoiesis in fatty marrow. Blood. 1974;43(1):33–8.

    CAS  PubMed  Google Scholar 

  5. •• Tavassoli M. Marrow adipose cells. Histochemical identification of labile and stable components. Arch Pathol Lab Med. 1976;100(1):16–8. Original reference for the dual bone marrow adipose tissue hypothesis.

    CAS  PubMed  Google Scholar 

  6. Bornstein S, Brown SA, Le PT, Wang X, DeMambro V, Horowitz MC, et al. FGF-21 and skeletal remodeling during and after lactation in C57BL/6J mice. Endocrinology. 2014;155(9):3516–26. https://doi.org/10.1210/en.2014-1083.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Cawthorn WP, Scheller EL. Editorial bone marrow adipose tissue: formation, function, and impact on health and disease. Front Endocrinol (Lausanne). 2017;8:112.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Hardouin P, Rharass T, Lucas S. Bone marrow adipose tissue: to be or not to be a typical adipose tissue? Front Endocrinol (Lausanne). 2016;7:85.

    Google Scholar 

  9. Scheller EL, Rosen CJ. What’s the matter with MAT? Marrow adipose tissue, metabolism, and skeletal health. Ann N Y Acad Sci. 2014 Apr;1311(1):14–30. https://doi.org/10.1111/nyas.12327.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Bigelow CL, Tavassoli M. Fatty involution of bone marrow in rabbits. Acta Anat (Basel). 1984;118(1):60–4. https://doi.org/10.1159/000145823.

    Article  CAS  Google Scholar 

  11. Cawthorn WP, Scheller EL, Parlee SD, Pham HA, Learman BS, Redshaw CM, et al. Expansion of bone marrow adipose tissue during caloric restriction is associated with increased circulating glucocorticoids and not with hypoleptinemia. Endocrinology. 2016;157(2):508–21. https://doi.org/10.1210/en.2015-1477.

    Article  CAS  PubMed  Google Scholar 

  12. Kricun ME. Red-yellow marrow conversion: its effect on the location of some solitary bone lesions. Skelet Radiol. 1985;14(1):10–9. https://doi.org/10.1007/BF00361188.

    Article  CAS  Google Scholar 

  13. • Robles H, Park S, Joens M, Fitzpatrick J, Craft CS, Scheller EL. Characterization of the bone marrow adipocyte niche with three-dimensional electron microscopy. Bone. 2018; https://doi.org/10.1016/j.bone.2018.01.020. High-resolution visualization of the rBMA and cBMA niche.

  14. Craft CS, Scheller EL. Evolution of the marrow adipose tissue microenvironment. Calcif Tissue Int. 2016;100(5):1–15.

    Google Scholar 

  15. Tavassoli M, Crosby WH. Bone marrow histogenesis: a comparison of fatty and red marrow. Science. 1970;169(3942):291–3. https://doi.org/10.1126/science.169.3942.291.

    Article  CAS  PubMed  Google Scholar 

  16. Tavassoli M. Hemopoiesis in ectopically implanted bone marrow. Kroc Found Ser. 1984;18:31–54.

    CAS  PubMed  Google Scholar 

  17. Biermann A, Graf von Keyserlingk D. Ultrastructure of reticulum cells in the bone marrow. Acta Anat (Basel). 1978;100(1):34–43. https://doi.org/10.1159/000144879.

    Article  CAS  Google Scholar 

  18. • 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):771–784.e6. Definition of the BMA progenitor. https://doi.org/10.1016/j.stem.2017.02.009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Mizoguchi T, Pinho S, Ahmed J, Kunisaki Y, Hanoun M, Mendelson A, et al. Osterix marks distinct waves of primitive and definitive stromal progenitors during bone marrow development. Dev Cell. 2014;29(3):340–9. https://doi.org/10.1016/j.devcel.2014.03.013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Zhou BO, Yue R, Murphy MM, Peyer JG, Morrison SJ. Leptin-receptor-expressing mesenchymal stromal cells represent the main source of bone formed by adult bone marrow. Cell Stem Cell. 2014;15(2):154–68. https://doi.org/10.1016/j.stem.2014.06.008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. 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.

    PubMed  PubMed Central  Google Scholar 

  22. Emery JL, Follett GF. Regression of bone-marrow haemopoiesis from the terminal digits in the foetus and infant. Br J Haematol. 1964;10(4):485–9. https://doi.org/10.1111/j.1365-2141.1964.tb00725.x.

    Article  CAS  PubMed  Google Scholar 

  23. • 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. The BMA supports myelo-erythropoiesis and hematopoietic equilibrium.

    Article  CAS  PubMed  Google Scholar 

  24. Gesta S, Tseng YH, Kahn CR. Developmental origin of fat: tracking obesity to its source. Cell. 2007 Oct 19;131(2):242–56. https://doi.org/10.1016/j.cell.2007.10.004.

    Article  CAS  PubMed  Google Scholar 

  25. Pond CM. The evolution of mammalian adipose tissue. In: Symonds ME, editor. Adipose Tissue Biology. New York: Springer New York; 2012. p. 227–69.

    Chapter  Google Scholar 

  26. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Devlin MJ, Cloutier AM, Thomas NA, Panus DA, Lotinun S, Pinz I, et al. Caloric restriction leads to high marrow adiposity and low bone mass in growing mice. J Bone Miner Res. 2010;25(9):2078–88. https://doi.org/10.1002/jbmr.82.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Tavassoli M. Differential response of bone marrow and extramedullary adipose cells to starvation. Experientia. 1974;30(4):424–5. https://doi.org/10.1007/BF01921701.

    Article  CAS  PubMed  Google Scholar 

  29. Bathija A, Davis S, Trubowitz S. Bone marrow adipose tissue: response to acute starvation. Am J Hematol. 1979;6(3):191–8. https://doi.org/10.1002/ajh.2830060303.

    Article  CAS  PubMed  Google Scholar 

  30. Devlin MJ. Why does starvation make bones fat? Am J Hum Biol. 2011;23(5):577–85. https://doi.org/10.1002/ajhb.21202.

    Article  PubMed  PubMed Central  Google Scholar 

  31. 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. 2018;233(2):1500–11. https://doi.org/10.1002/jcp.26037.

    Article  CAS  PubMed  Google Scholar 

  32. • 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. BMAs secrete factors which support hematopoiesis.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Bigelow CL, Tavassoli M. Studies on conversion of yellow marrow to red marrow by using ectopic bone marrow implants. Exp Hematol. 1984;12(7):581–5.

    CAS  PubMed  Google Scholar 

  34. Maniatis A, Tavassoli M, Crosby WH. Factors affecting the conversion of yellow to red marrow. Blood. 1971;37(5):581–6.

    CAS  PubMed  Google Scholar 

  35. Tavassoli M. Marrow adipose cells. Ultrastructural and histochemical characterization. Arch Pathol. 1974;98(3):189–92.

    CAS  PubMed  Google Scholar 

  36. Tavassoli M. Ultrastructural development of bone marrow adipose cell. Acta Anat (Basel). 1976;94(1):65–77. https://doi.org/10.1159/000144545.

    Article  CAS  Google Scholar 

  37. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. 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.

    CAS  Google Scholar 

  39. Tran MA, Lac DT, Berlan M, Lafontan M. Interplay of alpha-2 and beta adrenoceptors in the control of free fatty acid release from bone marrow adipose tissue. J Pharmacol Exp Ther. 1984;230(1):228–31.

    CAS  PubMed  Google Scholar 

  40. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Blanchette-Mackie EJ, Scow RO. Lipolysis and lamellar structures in white adipose tissue of young rats: lipid movement in membranes. J Ultrastruct Res. 1981;77(3):295–318. https://doi.org/10.1016/S0022-5320(81)80026-3.

    Article  CAS  PubMed  Google Scholar 

  43. Qiang G, Whang Kong H, Xu S, Pham HA, Parlee SD, Burr AA, et al. Lipodystrophy and severe metabolic dysfunction in mice with adipose tissue-specific insulin receptor ablation. Mol Metab. 2016;5(7):480–90. https://doi.org/10.1016/j.molmet.2016.05.005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Patsch JM, Li X, Baum T, Yap SP, Karampinos DC, Schwartz AV, et al. Bone marrow fat composition as a novel imaging biomarker in postmenopausal women with prevalent fragility fractures. J Bone Miner Res. 2013;28(8):1721–8. https://doi.org/10.1002/jbmr.1950.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Yeung DK, Griffith JF, Antonio GE, Lee FK, Woo J, Leung PC. Osteoporosis is associated with increased marrow fat content and decreased marrow fat unsaturation: a proton MR spectroscopy study. J Magn Reson Imaging. 2005;22(2):279–85. https://doi.org/10.1002/jmri.20367.

    Article  PubMed  Google Scholar 

  46. Yu EW, Greenblatt L, Eajazi A, Torriani M, Bredella MA. Marrow adipose tissue composition in adults with morbid obesity. Bone. 2017;97:38–42. https://doi.org/10.1016/j.bone.2016.12.018.

    Article  CAS  PubMed  Google Scholar 

  47. Pino AM, Miranda M, Figueroa C, Rodríguez JP, Rosen CJ. Qualitative aspects of bone marrow adiposity in osteoporosis. Front Endocrinol (Lausanne). 2016;7:139.

    PubMed  PubMed Central  Google Scholar 

  48. Liu LF, Shen WJ, Ueno M, Patel S, Kraemer FB. Characterization of age-related gene expression profiling in bone marrow and epididymal adipocytes. BMC Genomics. 2011;12(1):212. https://doi.org/10.1186/1471-2164-12-212.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Liu LF, Shen WJ, Ueno M, Patel S, Azhar S, Kraemer FB. Age-related modulation of the effects of obesity on gene expression profiles of mouse bone marrow and epididymal adipocytes. PLoS One. 2013;8(8):e72367. https://doi.org/10.1371/journal.pone.0072367.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Poloni A, Maurizi G, Serrani F, Mancini S, Zingaretti MC, Frontini A, et al. Molecular and functional characterization of human bone marrow adipocytes. Exp Hematol. 2013;41(6):558–566.e2. https://doi.org/10.1016/j.exphem.2013.02.005.

    Article  CAS  PubMed  Google Scholar 

  51. 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.

    Article  CAS  PubMed  Google Scholar 

  52. Lecka-Czernik B, Stechschulte LA, Czernik PJ, Sherman SB, Huang S, Krings A. Marrow adipose tissue: skeletal location, sexual dimorphism, and response to sex steroid deficiency. Front Endocrinol (Lausanne). 2017;8:188. https://doi.org/10.3389/fendo.2017.00188.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Tencerova M, Kassem M. The bone marrow-derived stromal cells: commitment and regulation of adipogenesis. Front Endocrinol (Lausanne). 2016;7:127.

    PubMed  PubMed Central  Google Scholar 

  54. Ge C, Zhao G, Li B, Li Y, Cawthorn WP, MacDougald OA, et al. Genetic inhibition of PPARγ S112 phosphorylation reduces bone formation and stimulates marrow adipogenesis. Bone. 2018;107:1–9. https://doi.org/10.1016/j.bone.2017.10.023.

    Article  CAS  PubMed  Google Scholar 

  55. • 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. BMAs can secrete bone-modifying factors including RANKL

    Article  CAS  PubMed  Google Scholar 

  56. Liu LF, Shen WJ, Zhang ZH, Wang LJ, Kraemer FB. Adipocytes decrease Runx2 expression in osteoblastic cells: roles of PPARγ and adiponectin. J Cell Physiol. 2010;225(3):837–45. https://doi.org/10.1002/jcp.22291.

    Article  CAS  PubMed  Google Scholar 

  57. •• Lu W, Weng W, Zhu Q, Zhai Y, Wan Y, Liu H, et al. Small bone marrow adipocytes predict poor prognosis in acute myeloid leukemia. Haematologica. 2018;103(1):e21–4. Utilization of lipid from BMAs may predict poor clinical prognosis of malignancy.

Download references

Funding

This work was funded by the National Institutes of Health including a pilot grant from the Washington University Musculoskeletal Research Center P30-AR057235 (C.S.C.), R24-DK092759 (O.A.M.), and R00-DE024178 (E.L.S.).

Author information

Authors and Affiliations

  1. Division of Bone and Mineral Diseases, Department of Internal Medicine, Washington University, Saint Louis, MO, USA

    Clarissa S Craft & Erica L Scheller

  2. Department of Cell Biology & Physiology, Washington University, St. Louis, MO, USA

    Clarissa S Craft & Erica L Scheller

  3. Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA

    Ziru Li & Ormond A MacDougald

Authors
  1. Clarissa S Craft
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ziru Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ormond A MacDougald
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Erica L Scheller
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Erica L Scheller.

Ethics declarations

Conflict of Interest

Clarissa S. Craft, Ziru Li, Ormond A. MacDougald, and Erica L. Scheller each declare no conflicts 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.

Additional information

This article is part of the Topical Collection on Molecular Biology of Bone Marrow Fat Adiposity

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Craft, C.S., Li, Z., MacDougald, O.A. et al. Molecular Differences Between Subtypes of Bone Marrow Adipocytes. Curr Mol Bio Rep 4, 16–23 (2018). https://doi.org/10.1007/s40610-018-0087-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40610-018-0087-9

Keywords

Search

Navigation