Ewha Med J.  2022 Jan;45(1):11-16. 10.12771/emj.2022.45.1.11.

The Role of Bone Marrow Adipose Tissue in Health and Disease

Affiliations
  • 1Advanced Biomedical Research Institute, Ewha Womans University Seoul Hospital, Seoul, Korea

Abstract

Bone marrow adipose tissue (BMAT) increases with aging and once disregarded as a passive marrow space filler. However, accumulating evidence suggests that BMAT is an active modulator of bone, hematopoiesis, and metabolism. Characterization of BMAT in molecular and cellular levels identified that it is distinct from white or brown adipose tissue. This review summarizes current knowledge on changes of BMAT under physiological and pathophysiological conditions of bone and marrow. Expansion of BMAT is closely linked with increased fracture risk, therefore regulation of BMAT can be considered as a novel therapeutic approach to enhance bone strength. Regarding hematopoiesis, increase in BMAT is negatively associated with the marrow function, but it is indispensable for maintaining myelopoiesis in acute myeloid leukemia. In addition, BMAT expansion is paradoxically identified in obesity as well as anorexia nervosa. It is considered that BMAT performs a different function in different nutritional states. Future studies would involve more detailed research about regulatory factors of BMAT and its functions in health and diseases. Enhancing our understanding about BMAT would open a new avenue for combating BMAT-related diseases.

Keyword

Anorexia nervosa; Bone marrow; Hematopoiesis; Obesity; Osteoporosis

Reference

1. Kricun ME. 1985; Red-yellow marrow conversion: its effect on the location of some solitary bone lesions. Skeletal Radiol. 14:10–19. DOI: 10.1007/BF00361188. PMID: 3895447.
Article
2. Justesen J, Stenderup K, Ebbesen EN, Mosekilde L, Steiniche T, Kassem M. 2001; Adipocyte tissue volume in bone marrow is increased with aging and in patients with osteoporosis. Biogerontology. 2:165–171. DOI: 10.1023/A:1011513223894. PMID: 11708718.
3. Schwartz AV, Sigurdsson S, Hue TF, Lang TF, Harris TB, Rosen CJ, et al. 2013; Vertebral bone marrow fat associated with lower trabecular BMD and prevalent vertebral fracture in older adults. J Clin Endocrinol Metab. 98:2294–2300. DOI: 10.1210/jc.2012-3949. PMID: 23553860. PMCID: PMC3667265.
Article
4. Fazeli PK, Horowitz MC, MacDougald OA, Scheller EL, Rodeheffer MS, Rosen CJ, et al. 2013; Marrow fat and bone: new perspectives. J Clin Endocrinol Metab. 98:935–945. DOI: 10.1210/jc.2012-3634. PMID: 23393168. PMCID: PMC3590487.
5. Piotrowska K, Tarnowski M. 2021; Bone marrow adipocytes: role in physiology and various nutritional conditions in human and animal models. Nutrients. 13:1412. DOI: 10.3390/nu13051412. PMID: 33922353. PMCID: PMC8146898.
Article
6. Tratwal J, Rojas-Sutterlin S, Bataclan C, Blum S, Naveiras O. 2021; Bone marrow adiposity and the hematopoietic niche: a historical perspective of reciprocity, heterogeneity, and lineage commitment. Best Pract Res Clin Endocrinol Metab. 35:101564. DOI: 10.1016/j.beem.2021.101564. PMID: 34417114.
Article
7. Stockman R. 1898; The action of arsenic on the bone-marrow and blood. J Physiol. 23:376–382. DOI: 10.1113/jphysiol.1898.sp000734. PMID: 16992464. PMCID: PMC1516520.
8. Yeung DK, Griffith JF, Antonio GE, Lee FK, Woo J, Leung PC. 2005; Osteoporosis is associated with increased marrow fat content and decreased marrow fat unsaturation: a proton MR spectroscopy study. J Magn Reson Imaging. 22:279–285. DOI: 10.1002/jmri.20367. PMID: 16028245.
Article
9. Cawthorn WP, Scheller EL, Learman BS, Parlee SD, Simon BR, Mori H, et al. 2014; Bone marrow adipose tissue is an endocrine organ that contributes to increased circulating adiponectin during caloric restriction. Cell Metab. 20:368–375. DOI: 10.1016/j.cmet.2014.06.003. PMID: 24998914. PMCID: PMC4126847.
Article
10. Botolin S, McCabe LR. 2007; Bone loss and increased bone adiposity in spontaneous and pharmacologically induced diabetic mice. Endocrinology. 148:198–205. DOI: 10.1210/en.2006-1006. PMID: 17053023.
Article
11. Ambrosi TH, Scialdone A, Graja A, Gohlke S, Jank AM, Bocian C, et al. 2017; Adipocyte accumulation in the bone marrow during obesity and aging impairs stem cell-based hematopoietic and bone regeneration. Cell Stem Cell. 20:771–784. DOI: 10.1016/j.stem.2017.02.009. PMID: 28330582. PMCID: PMC5459794.
Article
12. Kim YH, Cho KA, Lee HJ, Park M, Shin SJ, Park JW, et al. 2020; Conditioned medium from human tonsil-derived mesenchymal stem cells enhances bone marrow engraftment via endothelial cell restoration by pleiotrophin. Cells. 9:221. DOI: 10.3390/cells9010221. PMID: 31952360. PMCID: PMC7017309.
Article
13. Hui SK, Sharkey L, Kidder LS, Zhang Y, Fairchild G, Coghill K, et al. 2012; The influence of therapeutic radiation on the patterns of bone marrow in ovary-intact and ovariectomized mice. PLoS One. 7:e42668. DOI: 10.1371/journal.pone.0042668. PMID: 22880075. PMCID: PMC3412808.
Article
14. Cawthorn WP, Scheller EL, Parlee SD, Pham HA, Learman BS, Redshaw CM, et al. 2016; Expansion of bone marrow adipose tissue during caloric restriction is associated with increased circulating glucocorticoids and not with hypoleptinemia. Endocrinology. 157:508–521. DOI: 10.1210/en.2015-1477. PMID: 26696121. PMCID: PMC4733126.
Article
15. Trubowitz S, Bathija A. 1977; Cell size and plamitate-1-14c turnover of rabbit marrow fat. Blood. 49:599–605. DOI: 10.1182/blood.V49.4.599.599. PMID: 843618.
Article
16. Griffith JF, Yeung DK, Ahuja AT, Choy CW, Mei WY, Lam SS, et al. 2009; A study of bone marrow and subcutaneous fatty acid composition in subjects of varying bone mineral density. Bone. 44:1092–1096. DOI: 10.1016/j.bone.2009.02.022. PMID: 19268721.
Article
17. Suchacki KJ, Tavares AA, Mattiucci D, Scheller EL, Papanastasiou G, Gray C, et al. 2020; Bone marrow adipose tissue is a unique adipose subtype with distinct roles in glucose homeostasis. Nat Commun. 11:3097. DOI: 10.1038/s41467-020-16878-2. PMID: 32555194. PMCID: PMC7303125.
Article
18. Schellinger D, Lin CS, Hatipoglu HG, Fertikh D. 2001; Potential value of vertebral proton MR spectroscopy in determining bone weakness. AJNR Am J Neuroradiol. 22:1620–1627. PMID: 11559519. PMCID: PMC7974571.
19. Tencerova M, Kassem M. 2016; The bone marrow-derived stromal cells: commitment and regulation of adipogenesis. Front Endocrinol (Lausanne). 7:127. DOI: 10.3389/fendo.2016.00127. PMID: 27708616. PMCID: PMC5030474.
Article
20. Fan Q, Tang T, Zhang X, Dai K. 2009; The role of CCAAT/enhancer binding protein (C/EBP)-alpha in osteogenesis of C3H10T1/2 cells induced by BMP-2. J Cell Mol Med. 13(8B):2489–2505. DOI: 10.1111/j.1582-4934.2008.00606.x. PMID: 19120697. PMCID: PMC6529959.
Article
21. Li Y, Jin D, Xie W, Wen L, Chen W, Xu J, et al. 2018; PPAR-γ and Wnt regulate the differentiation of MSCs into adipocytes and osteoblasts respectively. Curr Stem Cell Res Ther. 13:185–192. DOI: 10.2174/1574888X12666171012141908. PMID: 29034841.
Article
22. Li J, Zhang N, Huang X, Xu J, Fernandes JC, Dai K, et al. 2013; Dexamethasone shifts bone marrow stromal cells from osteoblasts to adipocytes by C/EBPalpha promoter methylation. Cell Death Dis. 4:e832. DOI: 10.1038/cddis.2013.348. PMID: 24091675. PMCID: PMC3824658.
Article
23. van Bezooijen RL, Roelen BA, Visser A, van der Wee-Pals L, de Wilt E, Karperien M, et al. 2004; Sclerostin is an osteocyte-expressed negative regulator of bone formation, but not a classical BMP antagonist. J Exp Med. 199:805–814. DOI: 10.1084/jem.20031454. PMID: 15024046. PMCID: PMC2212719.
Article
24. Ominsky MS, Vlasseros F, Jolette J, Smith SY, Stouch B, Doellgast G, et al. 2010; Two doses of sclerostin antibody in cynomolgus monkeys increases bone formation, bone mineral density, and bone strength. J Bone Miner Res. 25:948–959. DOI: 10.1002/jbmr.14. PMID: 20200929.
Article
25. McClung MR, Grauer A, Boonen S, Bolognese MA, Brown JP, Diez-Perez A, et al. 2014; Romosozumab in postmenopausal women with low bone mineral density. N Engl J Med. 370:412–420. DOI: 10.1056/NEJMoa1305224. PMID: 24382002.
Article
26. Kim YH, Park M, Cho KA, Kim BK, Ryu JH, Woo SY, et al. 2016; Tonsil-derived mesenchymal stem cells promote bone mineralization and reduce marrow and visceral adiposity in a mouse model of senile osteoporosis. Stem Cells Dev. 25:1161–1171. DOI: 10.1089/scd.2016.0063. PMID: 27245267.
Article
27. Botolin S, McCabe LR. 2006; Inhibition of PPARgamma prevents type I diabetic bone marrow adiposity but not bone loss. J Cell Physiol. 209:967–976. DOI: 10.1002/jcp.20804. PMID: 16972249.
Article
28. Liu LF, Shen WJ, Ueno M, Patel S, Kraemer FB. 2011; Characterization of age-related gene expression profiling in bone marrow and epididymal adipocytes. BMC Genomics. 12:212. DOI: 10.1186/1471-2164-12-212. PMID: 21545734. PMCID: PMC3113784.
Article
29. Monami M, Dicembrini I, Antenore A, Mannucci E. 2011; Dipeptidyl peptidase-4 inhibitors and bone fractures: a meta-analysis of randomized clinical trials. Diabetes Care. 34:2474–2476. DOI: 10.2337/dc11-1099. PMID: 22025784. PMCID: PMC3198283.
30. Polineni S, Resulaj M, Faje AT, Meenaghan E, Bredella MA, Bouxsein M, et al. 2020; Red and white blood cell counts are associated with bone marrow adipose tissue, bone mineral density, and bone microarchitecture in premenopausal women. J Bone Miner Res. 35:1031–1039. DOI: 10.1002/jbmr.3986. PMID: 32078187. PMCID: PMC7881438.
Article
31. Li Z, Hardij J, Evers SS, Hutch CR, Choi SM, Shao Y, et al. 2019; G-CSF partially mediates effects of sleeve gastrectomy on the bone marrow niche. J Clin Invest. 129:2404–2416. DOI: 10.1172/JCI126173. PMID: 31063988. PMCID: PMC6546463.
Article
32. Yamazaki K, Allen TD. 1991; Ultrastructural and morphometric alterations in bone marrow stromal tissue after 7 Gy irradiation. Blood Cells. 17:527–549. PMID: 1760560.
33. Naveiras O, Nardi V, Wenzel PL, Hauschka PV, Fahey F, Daley GQ. 2009; Bone-marrow adipocytes as negative regulators of the haematopoietic microenvironment. Nature. 460:259–263. DOI: 10.1038/nature08099. PMID: 19516257. PMCID: PMC2831539.
Article
34. Ferland-McCollough D, Maselli D, Spinetti G, Sambataro M, Sullivan N, Blom A, et al. 2018; MCP-1 feedback loop between adipocytes and mesenchymal stromal cells causes fat accumulation and contributes to hematopoietic stem cell rarefaction in the bone marrow of patients with diabetes. Diabetes. 67:1380–1394. DOI: 10.2337/db18-0044. PMID: 29703845.
Article
35. Tikhonova AN, Dolgalev I, Hu H, Sivaraj KK, Hoxha E, Cuesta-Dominguez A, et al. 2019; The bone marrow microenvironment at single-cell resolution. Nature. 569:222–228. DOI: 10.1038/s41586-019-1104-8. PMID: 30971824. PMCID: PMC6607432.
Article
36. Baccin C, Al-Sabah J, Velten L, Helbling PM, Grunschlager F, Hernandez-Malmierca P, et al. 2020; Combined single-cell and spatial transcriptomics reveal the molecular, cellular and spatial bone marrow niche organization. Nat Cell Biol. 22:38–48. DOI: 10.1038/s41556-019-0439-6. PMID: 31871321. PMCID: PMC7610809.
Article
37. Boyd AL, Reid JC, Salci KR, Aslostovar L, Benoit YD, Shapovalova Z, et al. 2017; Acute myeloid leukaemia disrupts endogenous myelo-erythropoiesis by compromising the adipocyte bone marrow niche. Nat Cell Biol. 19:1336–1347. DOI: 10.1038/ncb3625. PMID: 29035359.
Article
38. Shafat MS, Oellerich T, Mohr S, Robinson SD, Edwards DR, Marlein CR, et al. 2017; Leukemic blasts program bone marrow adipocytes to generate a protumoral microenvironment. Blood. 129:1320–1332. DOI: 10.1182/blood-2016-08-734798. PMID: 28049638.
Article
39. Herroon MK, Rajagurubandara E, Hardaway AL, Powell K, Turchick A, Feldmann D, et al. 2013; Bone marrow adipocytes promote tumor growth in bone via FABP4-dependent mechanisms. Oncotarget. 4:2108–2123. DOI: 10.18632/oncotarget.1482. PMID: 24240026. PMCID: PMC3875773.
Article
40. Bredella MA, Torriani M, Ghomi RH, Thomas BJ, Brick DJ, Gerweck AV, et al. 2011; Vertebral bone marrow fat is positively associated with visceral fat and inversely associated with IGF-1 in obese women. Obesity (Silver Spring). 19:49–53. DOI: 10.1038/oby.2010.106. PMID: 20467419. PMCID: PMC3593350.
Article
41. L Newton A, J Hanks L, Davis M, Casazza K. 2013; The relationships among total body fat, bone mineral content and bone marrow adipose tissue in early-pubertal girls. Bonekey Rep. 2:315. DOI: 10.1038/bonekey.2013.49. PMID: 23951544. PMCID: PMC3722749.
Article
42. de Araujo IM, Salmon CE, Nahas AK, Nogueira-Barbosa MH, Elias J Jr, de Paula FJ. 2017; Marrow adipose tissue spectrum in obesity and type 2 diabetes mellitus. Eur J Endocrinol. 176:21–30. DOI: 10.1530/EJE-16-0448. PMID: 27707768.
Article
43. de Paula FJ, de Araujo IM, Carvalho AL, Elias J Jr, Salmon CE, Nogueira-Barbosa MH. 2015; The relationship of fat distribution and insulin resistance with lumbar spine bone mass in women. PLoS One. 10:e0129764. DOI: 10.1371/journal.pone.0129764. PMID: 26067489. PMCID: PMC4466243.
Article
44. Bredella MA, Gill CM, Gerweck AV, Landa MG, Kumar V, Daley SM, et al. 2013; Ectopic and serum lipid levels are positively associated with bone marrow fat in obesity. Radiology. 269:534–541. DOI: 10.1148/radiol.13130375. PMID: 23861502. PMCID: PMC3807082.
Article
45. Tencerova M, Figeac F, Ditzel N, Taipaleenmaki H, Nielsen TK, Kassem M. 2018; High-fat diet-induced obesity promotes expansion of bone marrow adipose tissue and impairs skeletal stem cell functions in mice. J Bone Miner Res. 33:1154–1165. DOI: 10.1002/jbmr.3408. PMID: 29444341.
Article
46. Tencerova M, Frost M, Figeac F, Nielsen TK, Ali D, Lauterlein JL, et al. 2019; Obesity-associated hypermetabolism and accelerated senescence of bone marrow stromal stem cells suggest a potential mechanism for bone fragility. Cell Rep. 27:2050–2062. DOI: 10.1016/j.celrep.2019.04.066. PMID: 31091445.
Article
47. Bredella MA, Fazeli PK, Daley SM, Miller KK, Rosen CJ, Klibanski A, et al. 2014; Marrow fat composition in anorexia nervosa. Bone. 66:199–204. DOI: 10.1016/j.bone.2014.06.014. PMID: 24953711. PMCID: PMC4125432.
Article
48. Abella E, Feliu E, Granada I, Milla F, Oriol A, Ribera JM, et al. 2002; Bone marrow changes in anorexia nervosa are correlated with the amount of weight loss and not with other clinical findings. Am J Clin Pathol. 118:582–588. DOI: 10.1309/2Y7X-YDXK-006B-XLT2. PMID: 12375646.
Article
49. Fazeli PK, Bredella MA, Freedman L, Thomas BJ, Breggia A, Meenaghan E, et al. 2012; Marrow fat and preadipocyte factor-1 levels decrease with recovery in women with anorexia nervosa. J Bone Miner Res. 27:1864–1871. DOI: 10.1002/jbmr.1640. PMID: 22508185. PMCID: PMC3415584.
Article
50. Ecklund K, Vajapeyam S, Mulkern RV, Feldman HA, O'Donnell JM, DiVasta AD, et al. 2017; Bone marrow fat content in 70 adolescent girls with anorexia nervosa: magnetic resonance imaging and magnetic resonance spectroscopy assessment. Pediatr Radiol. 47:952–962. DOI: 10.1007/s00247-017-3856-3. PMID: 28432403. PMCID: PMC5650065.
Article
Full Text Links
  • EMJ
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr