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Obesity-Induced Changes in Bone Marrow Homeostasis

. 2020 ; 11 () : 294. [epub] 20200512

Language English Country Switzerland Media electronic-ecollection

Document type Journal Article, Research Support, Non-U.S. Gov't, Review

Obesity is characterized by low-grade inflammation, which is accompanied by increased accumulation of immune cells in peripheral tissues including adipose tissue (AT), skeletal muscle, liver and pancreas, thereby impairing their primary metabolic functions in the regulation of glucose homeostasis. Obesity has also shown to have a detrimental effect on bone homeostasis by altering bone marrow and hematopoietic stem cell differentiation and thus impairing bone integrity and immune cell properties. The origin of immune cells arises in the bone marrow, which has been shown to be affected with the obesogenic condition via increased cellularity and shifting differentiation and function of hematopoietic and bone marrow mesenchymal stem cells in favor of myeloid progenitors and increased bone marrow adiposity. These obesity-induced changes in the bone marrow microenvironment lead to dramatic bone marrow remodeling and compromising immune cell functions, which in turn affect systemic inflammatory conditions and regulation of whole-body metabolism. However, there is limited information on the inflammatory secretory factors creating the bone marrow microenvironment and how these factors changed during metabolic complications. This review summarizes recent findings on inflammatory and cellular changes in the bone marrow in relation to obesity and further discuss whether dietary intervention or physical activity may have beneficial effects on the bone marrow microenvironment and whole-body metabolism.

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Hindorf C, Glatting G, Chiesa C, Linden O, Flux G, Committee ED. EANM Dosimetry Committee guidelines for bone marrow and whole-body dosimetry. Eur J Nucl Med Mol Imaging. (2010) 37:1238–50. 10.1007/s00259-010-1422-4 PubMed DOI

Greer JP. Windrobe's Clinical Hematology, 14th ed. Philadelphia: Wolters Kluwer; (2019). p. 1–2312.

Zhao E, Xu H, Wang L, Kryczek I, Wu K, Hu Y, et al. . Bone marrow and the control of immunity. Cell Mol Immunol. (2012) 9:11–9. 10.1038/cmi.2011.47 PubMed DOI PMC

Tencerova M, Kassem M. The bone marrow-derived stromal cells: commitment and regulation of adipogenesis. Front Endocrinol. (2016) 7:127. 10.3389/fendo.2016.00127 PubMed DOI PMC

Schneider RK, Puellen A, Kramann R, Raupach K, Bornemann J, Knuechel R, et al. . The osteogenic differentiation of adult bone marrow and perinatal umbilical mesenchymal stem cells and matrix remodelling in three-dimensional collagen scaffolds. Biomaterials. (2010) 31:467–80. 10.1016/j.biomaterials.2009.09.059 PubMed DOI

Zhang ZY, Teoh SH, Chong MS, Lee ES, Tan LG, Mattar CN, et al. . Neo-vascularization and bone formation mediated by fetal mesenchymal stem cell tissue-engineered bone grafts in critical-size femoral defects. Biomaterials. (2010) 31:608–20. 10.1016/j.biomaterials.2009.09.078 PubMed DOI

Yin T, Li L. The stem cell niches in bone. J Clin Invest. (2006) 116:1195–201. 10.1172/JCI28568 PubMed DOI PMC

Lemoli RM, D'Addio A. Hematopoietic stem cell mobilization. Haematologica. (2008) 93:321–4. 10.3324/haematol.12616 PubMed DOI

Cottler-Fox MH, Lapidot T, Petit I, Kollet O, DiPersio JF, Link D, et al. Stem cell mobilization. Hematol Am Soc Hematol Educ Prog. (2003) 419–37. 10.1182/asheducation-2003.1.419 PubMed DOI

Sahin AO, Buitenhuis M. Molecular mechanisms underlying adhesion and migration of hematopoietic stem cells. Cell Adh Migr. (2012) 6:39–48. 10.4161/cam.18975 PubMed DOI PMC

Mazo IB, Massberg S, von Andrian UH. Hematopoietic stem and progenitor cell trafficking. Trends Immunol. (2011) 32:493–503. 10.1016/j.it.2011.06.011 PubMed DOI PMC

Oliveira MC, Vullings J, van de Loo FAJ. Osteoporosis and osteoarthritis are two sides of the same coin paid for obesity. Nutrition. (2019) 70:110486. 10.1016/j.nut.2019.04.001 PubMed DOI

Caplan AI. Mesenchymal stem cells. J Orthop Res. (1991) 9:641–50. 10.1002/jor.1100090504 PubMed DOI

Feuerer M, Beckhove P, Mahnke Y, Hommel M, Kyewski B, Hamann A, et al. . Bone marrow microenvironment facilitating dendritic cell: CD4 T cell interactions and maintenance of CD4 memory. Int J Oncol. (2004) 25:867–76. 10.3892/ijo.25.4.867 PubMed DOI

Schirrmacher V, Feuerer M, Fournier P, Ahlert T, Umansky V, Beckhove P. T-cell priming in bone marrow: the potential for long-lasting protective anti-tumor immunity. Trends Mol Med. (2003) 9:526–34. 10.1016/j.molmed.2003.10.001 PubMed DOI

Minges Wols HA, Underhill GH, Kansas GS, Witte PL. The role of bone marrow-derived stromal cells in the maintenance of plasma cell longevity. J Immunol. (2002) 169:4213–21. 10.4049/jimmunol.169.8.4213 PubMed DOI

Zeng D, Gazit G, Dejbakhsh-Jones S, Balk SP, Snapper S, Taniguchi M, et al. . Heterogeneity of NK1.1+ T cells in the bone marrow: divergence from the thymus. J Immunol. (1999) 163:5338–45. PubMed

Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu YJ, et al. . Immunobiology of dendritic cells. Annu Rev Immunol. (2000) 18:767–811. 10.1146/annurev.immunol.18.1.767 PubMed DOI

Terstappen LW, Levin J. Bone marrow cell differential counts obtained by multidimensional flow cytometry. Blood Cells. (1992) 18:311–30. PubMed

Cartwright GE, Athens JW, Wintrobe MM. The kinetics of granulopoiesis in normal man. Blood. (1964) 24:780–803. 10.1182/blood.V24.6.780.780 PubMed DOI

Rankin SM. The bone marrow: a site of neutrophil clearance. J Leukoc Biol. (2010) 88:241–51. 10.1189/jlb.0210112 PubMed DOI

Shadduck RK, Waheed A, Wing EJ. Demonstration of a blood-bone marrow barrier to macrophage colony-stimulating factor. Blood. (1989) 73:68–73. 10.1182/blood.V73.1.68.68 PubMed DOI

Itkin T, Gur-Cohen S, Spencer JA, Schajnovitz A, Ramasamy SK, Kusumbe AP, et al. . Distinct bone marrow blood vessels differentially regulate haematopoiesis. Nature. (2016) 532:323–8. 10.1038/nature17624 PubMed DOI PMC

Kopp HG, Avecilla ST, Hooper AT, Rafii S. The bone marrow vascular niche: home of HSC differentiation and mobilization. Physiology. (2005) 20:349–56. 10.1152/physiol.00025.2005 PubMed DOI

Adler BJ, Kaushansky K, Rubin CT. Obesity-driven disruption of haematopoiesis and the bone marrow niche. Nat Rev Endocrinol. (2014) 10:737–48. 10.1038/nrendo.2014.169 PubMed DOI

Birbrair Frenette PS. Niche heterogeneity in the bone marrow. Ann N Y Acad Sci. (2016) 1370:82–96. 10.1111/nyas.13016 PubMed DOI PMC

Rharass T, Lucas S. Mechanisms in endocrinology: bone marrow adiposity and bone, a bad romance? Eur J Endocrinol. (2018) 179:R165–82. 10.1530/EJE-18-0182 PubMed DOI

Mendelson Frenette PS. Hematopoietic stem cell niche maintenance during homeostasis and regeneration. Nat Med. (2014) 20:833–46. 10.1038/nm.3647 PubMed DOI PMC

Wilson NK, Calero-Nieto FJ, Ferreira R, Gottgens B. Transcriptional regulation of haematopoietic transcription factors. Stem Cell Res Ther. (2011) 2:6. 10.1186/scrt47 PubMed DOI PMC

Wilson Murphy MJ, Oskarsson T, Kaloulis K, Bettess MD, Oser GM, et al. c-Myc controls the balance between hematopoietic stem cell self-renewal and differentiation. Genes Dev. (2004) 18:2747–63. 10.1101/gad.313104 PubMed DOI PMC

Smith LT, Hohaus S, Gonzalez DA, Dziennis SE, Tenen DG. PU.1 (Spi-1) and C/EBP alpha regulate the granulocyte colony-stimulating factor receptor promoter in myeloid cells. Blood. (1996) 88:1234–47. 10.1182/blood.V88.4.1234.bloodjournal8841234 PubMed DOI

Hohaus S, Petrovick MS, Voso MT, Sun Z, Zhang DE, Tenen DG. PU.1 (Spi-1) and C/EBP alpha regulate expression of the granulocyte-macrophage colony-stimulating factor receptor alpha gene. Mol Cell Biol. (1995) 15:5830–45. 10.1128/MCB.15.10.5830 PubMed DOI PMC

Zhang DE, Hetherington CJ, Chen HM, Tenen DG. The macrophage transcription factor PU.1 directs tissue-specific expression of the macrophage colony-stimulating factor receptor. Mol Cell Biol. (1994) 14:373–81. 10.1128/MCB.14.1.373 PubMed DOI PMC

Rothenberg EV, Hosokawa H, Ungerback J. Mechanisms of action of hematopoietic transcription factor PU.1 in initiation of T-cell development. Front Immunol. (2019) 10:228. 10.3389/fimmu.2019.00228 PubMed DOI PMC

Georgopoulos K, Bigby M, Wang JH, Molnar A, Wu P, Winandy S, et al. . The Ikaros gene is required for the development of all lymphoid lineages. Cell. (1994) 79:143–56. 10.1016/0092-8674(94)90407-3 PubMed DOI

Wang J, Sun Q, Morita Y, Jiang H, Gross A, Lechel A, et al. . A differentiation checkpoint limits hematopoietic stem cell self-renewal in response to DNA damage. Cell. (2012) 148:1001–14. 10.1016/j.cell.2012.01.040 PubMed DOI

Wang X, Dong F, Zhang S, Yang W, Yu W, Wang Z, et al. . TGF-beta1 negatively regulates the number and function of hematopoietic stem cells. Stem Cell Rep. (2018) 11:274–87. 10.1016/j.stemcr.2018.05.017 PubMed DOI PMC

Bresnick EH, Katsumura KR, Lee HY, Johnson KD, Perkins AS. Master regulatory GATA transcription factors: mechanistic principles and emerging links to hematologic malignancies. Nucleic Acids Res. (2012) 40:5819–31. 10.1093/nar/gks281 PubMed DOI PMC

Rizo Dontje B, Vellenga E, de Haan G, Schuringa JJ. Long-term maintenance of human hematopoietic stem/progenitor cells by expression of BMI1. Blood. (2008) 111:2621–30. 10.1182/blood-2007-08-106666 PubMed DOI

Rizo Olthof S, Han L, Vellenga E, de Haan G, Schuringa JJ. Repression of BMI1 in normal and leukemic human CD34(+) cells impairs self-renewal and induces apoptosis. Blood. (2009) 114:1498–505. 10.1182/blood-2009-03-209734 PubMed DOI

Lee JM, Govindarajah V, Goddard B, Hinge A, Muench DE, Filippi MD, et al. . Obesity alters the long-term fitness of the hematopoietic stem cell compartment through modulation of Gfi1 expression. J Exp Med. (2018) 215:627–44. 10.1084/jem.20170690 PubMed DOI PMC

Buisman SC, de Haan G. Epigenetic changes as a target in aging haematopoietic stem cells and age-related malignancies. Cells. (2019) 8:868. 10.3390/cells8080868 PubMed DOI PMC

Florian MC, Dorr K, Niebel A, Daria D, Schrezenmeier H, Rojewski M, et al. . Cdc42 activity regulates hematopoietic stem cell aging and rejuvenation. Cell Stem Cell. (2012) 10:520–30. 10.1016/j.stem.2012.04.007 PubMed DOI PMC

Chen X, Skutt-Kakaria K, Davison J, Ou YL, Choi E, Malik P, et al. . G9a/GLP-dependent histone H3K9me2 patterning during human hematopoietic stem cell lineage commitment. Genes Dev. (2012) 26:2499–511. 10.1101/gad.200329.112 PubMed DOI PMC

Trowbridge JJ, Snow JW, Kim J, Orkin SH. DNA methyltransferase 1 is essential for and uniquely regulates hematopoietic stem and progenitor cells. Cell Stem Cell. (2009) 5:442–9. 10.1016/j.stem.2009.08.016 PubMed DOI PMC

Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K, Deguchi K, et al. . Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell. (1997) 89:755–64. 10.1016/S0092-8674(00)80258-5 PubMed DOI

Nakashima K, Zhou X, Kunkel G, Zhang Z, Deng JM, Behringer RR, et al. . The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell. (2002) 108:17–29. 10.1016/S0092-8674(01)00622-5 PubMed DOI

Kamata M, Okitsu Y, Fujiwara T, Kanehira M, Nakajima S, Takahashi T, et al. . GATA2 regulates differentiation of bone marrow-derived mesenchymal stem cells. Haematologica. (2014) 99:1686–96. 10.3324/haematol.2014.105692 PubMed DOI PMC

Tolkachov Fischer C, Ambrosi TH, Bothe M, Han CT, Muenzner M, et al. . Loss of the hematopoietic stem cell factor GATA2 in the osteogenic lineage impairs trabecularization and mechanical strength of bone. Mol Cell Biol. (2018) 38:e00599-17. 10.1128/MCB.00599-17 PubMed DOI PMC

Muruganandan S, Roman AA, Sinal CJ. Adipocyte differentiation of bone marrow-derived mesenchymal stem cells: cross talk with the osteoblastogenic program. Cell Mol Life Sci. (2009) 66:236–53. 10.1007/s00018-008-8429-z PubMed DOI PMC

Cho HH, Park HT, Kim YJ, Bae YC, Suh KT, Jung JS. Induction of osteogenic differentiation of human mesenchymal stem cells by histone deacetylase inhibitors. J Cell Biochem. (2005) 96:533–42. 10.1002/jcb.20544 PubMed DOI

Schroeder TM, Westendorf JJ. Histone deacetylase inhibitors promote osteoblast maturation. J Bone Miner Res. (2005) 20:2254–63. 10.1359/JBMR.050813 PubMed DOI

Addison WN, Fu MM, Yang HX, Lin Z, Nagano K, Gori F, et al. . Direct transcriptional repression of Zfp423 by Zfp521 mediates a bone morphogenic protein-dependent osteoblast versus adipocyte lineage commitment switch. Mol Cell Biol. (2014) 34:3076–85. 10.1128/MCB.00185-14 PubMed DOI PMC

Liu A, Chen M, Kumar R, Stefanovic-Racic M, O'Doherty RM, Ding Y, et al. . Bone marrow lympho-myeloid malfunction in obesity requires precursor cell-autonomous TLR4. Nat Commun. (2018) 9:708. 10.1038/s41467-018-03145-8 PubMed DOI PMC

Lackey DE, Reis FCG, Isaac R, Zapata RC, El Ouarrat D, Lee YS, et al. . Adipocyte PU.1 knockout promotes insulin sensitivity in HFD-fed obese mice. Sci Rep. (2019) 9:14779. 10.1038/s41598-019-51196-8 PubMed DOI PMC

Lampreia FP, Carmelo JG, Anjos-Afonso F. Notch signaling in the regulation of hematopoietic stem cell. Curr Stem Cell Rep. (2017) 3:202–9. 10.1007/s40778-017-0090-8 PubMed DOI PMC

Sasaki T, Moro K, Kubota T, Kubota N, Kato T, Ohno H, et al. . Innate lymphoid cells in the induction of obesity. Cell Rep. (2019) 28:202–17 e7. 10.1016/j.celrep.2019.06.016 PubMed DOI

Zeng H, Yucel R, Kosan C, Klein-Hitpass L, Moroy T. Transcription factor Gfi1 regulates self-renewal and engraftment of hematopoietic stem cells. EMBO J. (2004) 23:4116–25. 10.1038/sj.emboj.7600419 PubMed DOI PMC

Tang EH, Shimizu K, Christen T, Rocha VZ, Shvartz E, Tesmenitsky Y, et al. . Lack of EP4 receptors on bone marrow-derived cells enhances inflammation in atherosclerotic lesions. Cardiovasc Res. (2011) 89:234–43. 10.1093/cvr/cvq262 PubMed DOI PMC

Tencerova M, Figeac F, Ditzel N, Taipaleenmaki H, Nielsen TK, Kassem M. High-fat diet-induced obesity promotes expansion of bone marrow adipose tissue and impairs skeletal stem cell functions in mice. J Bone Miner Res. (2018) 33:1154–65. 10.1002/jbmr.3408 PubMed DOI

Zhou Y, Guan X, Zhu Z, Gao S, Zhang C, Li C, et al. . Osteogenic differentiation of bone marrow-derived mesenchymal stromal cells on bone-derived scaffolds: effect of microvibration and role of ERK1/2 activation. Eur Cell Mater. (2011) 22:12–25. 10.22203/eCM.v022a02 PubMed DOI

Emmons R, Niemiro GM, De Lisio M. Hematopoiesis with obesity and exercise: role of the bone marrow niche. Exerc Immunol Rev. (2017) 23:82–95. 10.1155/2016/7131359 PubMed DOI

Lau E, Lee WD, Li J, Xiao A, Davies JE, Wu Q, et al. . Effect of low-magnitude, high-frequency vibration on osteogenic differentiation of rat mesenchymal stromal cells. J Orthop Res. (2011) 29:1075–80. 10.1002/jor.21334 PubMed DOI PMC

Zhao Q, Lu Y, Gan X, Yu H. Low magnitude high frequency vibration promotes adipogenic differentiation of bone marrow stem cells via P38 MAPK signal. PLoS ONE. (2017) 12:e0172954 10.1371/journal.pone.0172954 PubMed DOI PMC

Tontonoz P, Spiegelman BM. Fat and beyond: the diverse biology of PPARgamma. Annu Rev Biochem. (2008) 77:289–312. 10.1146/annurev.biochem.77.061307.091829 PubMed DOI

Hermetet F, Buffiere A, Aznague A, Pais de Barros JP, Bastie JN, Delva L, et al. . High-fat diet disturbs lipid raft/TGF-beta signaling-mediated maintenance of hematopoietic stem cells in mouse bone marrow. Nat Commun. (2019) 10:523. 10.1038/s41467-018-08228-0 PubMed DOI PMC

Roy B, Curtis ME, Fears LS, Nahashon SN, Fentress HM. Molecular mechanisms of obesity-induced osteoporosis and muscle atrophy. Front Physiol. (2016) 7:439. 10.3389/fphys.2016.00439 PubMed DOI PMC

Periyasamy-Thandavan S, Herberg S, Arounleut P, Upadhyay S, Dukes A, Davis C, et al. . Caloric restriction and the adipokine leptin alter the SDF-1 signaling axis in bone marrow and in bone marrow derived mesenchymal stem cells. Mol Cell Endocrinol. (2015) 410:64–72. 10.1016/j.mce.2015.03.001 PubMed DOI PMC

Klyushnenkova E, Mosca JD, Zernetkina V, Majumdar MK, Beggs KJ, Simonetti DW, et al. . T cell responses to allogeneic human mesenchymal stem cells: immunogenicity, tolerance, and suppression. J Biomed Sci. (2005) 12:47–57. 10.1007/s11373-004-8183-7 PubMed DOI

Di Nicola M, Carlo-Stella C, Magni M, Milanesi M, Longoni PD, Matteucci P, et al. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood. (2002) 99:3838–43. 10.1182/blood.V99.10.3838 PubMed DOI

Krampera M, Glennie S, Dyson J, Scott D, Laylor R, Simpson E, et al. . Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide. Blood. (2003) 101:3722–9. 10.1182/blood-2002-07-2104 PubMed DOI

Liang Jiang E, Yao J, Wang M, Chen S, Zhou Z, et al. Interferon-gamma mediates the immunosuppression of bone marrow mesenchymal stem cells on T-lymphocytes in vitro. Hematology. (2018) 23:44–9. 10.1080/10245332.2017.1333245 PubMed DOI

Corcione A, Benvenuto F, Ferretti E, Giunti D, Cappiello V, Cazzanti F, et al. . Human mesenchymal stem cells modulate B-cell functions. Blood. (2006) 107:367–72. 10.1182/blood-2005-07-2657 PubMed DOI

Jiang XX, Zhang Y, Liu B, Zhang SX, Wu Y, Yu XD, et al. . Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells. Blood. (2005) 105:4120–6. 10.1182/blood-2004-02-0586 PubMed DOI

Nauta AJ, Kruisselbrink AB, Lurvink E, Willemze R, Fibbe WE. Mesenchymal stem cells inhibit generation and function of both CD34+-derived and monocyte-derived dendritic cells. J Immunol. (2006) 177:2080–7. 10.4049/jimmunol.177.4.2080 PubMed DOI

Sotiropoulou PA, Perez SA, Gritzapis AD, Baxevanis CN, Papamichail M. Interactions between human mesenchymal stem cells and natural killer cells. Stem Cells. (2006) 24:74–85. 10.1634/stemcells.2004-0359 PubMed DOI

Spaggiari GM, Capobianco A, Abdelrazik H, Becchetti F, Mingari MC, Moretta L. Mesenchymal stem cells inhibit natural killer-cell proliferation, cytotoxicity, and cytokine production: role of indoleamine 2,3-dioxygenase and prostaglandin E2. Blood. (2008) 111:1327–33. 10.1182/blood-2007-02-074997 PubMed DOI

Horwitz EM, Prockop DJ, Fitzpatrick LA, Koo WW, Gordon PL, Neel M, et al. . Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Nat Med. (1999) 5:309–13. 10.1038/6529 PubMed DOI

Bang OY, Lee JS, Lee PH, Lee G. Autologous mesenchymal stem cell transplantation in stroke patients. Ann Neurol. (2005) 57:874–82. 10.1002/ana.20501 PubMed DOI

Carvello M, Lightner A, Yamamoto T, Kotze PG, Spinelli A. Mesenchymal stem cells for perianal Crohn's disease. Cells. (2019) 8:764. 10.3390/cells8070764 PubMed DOI PMC

Dige A, Hougaard HT, Agnholt J, Pedersen BG, Tencerova M, Kassem M, et al. . Efficacy of injection of freshly collected autologous adipose tissue into perianal fistulas in patients with Crohn's disease. Gastroenterology. (2019) 156:2208–16 e1. 10.1053/j.gastro.2019.02.005 PubMed DOI

Mollard RC, Gillam ME, Wood TM, Taylor CG, Weiler HA. (n-3) fatty acids reduce the release of prostaglandin E2 from bone but do not affect bone mass in obese (fa/fa) and lean Zucker rats. J Nutr. (2005) 135:499–504. 10.1093/jn/135.3.499 PubMed DOI

Miller JP, Izon D, DeMuth W, Gerstein R, Bhandoola A, Allman D. The earliest step in B lineage differentiation from common lymphoid progenitors is critically dependent upon interleukin 7. J Exp Med. (2002) 196:705–11. 10.1084/jem.20020784 PubMed DOI PMC

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:e90639. 10.1371/journal.pone.0090639 PubMed DOI PMC

Becker TC, Wherry EJ, Boone D, Murali-Krishna K, Antia R, Ma A, et al. . Interleukin 15 is required for proliferative renewal of virus-specific memory CD8 T cells. J Exp Med. (2002) 195:1541–8. 10.1084/jem.20020369 PubMed DOI PMC

Nielsen AR, Hojman P, Erikstrup C, Fischer CP, Plomgaard P, Mounier R, et al. . Association between interleukin-15 and obesity: interleukin-15 as a potential regulator of fat mass. J Clin Endocrinol Metab. (2008) 93:4486–93. 10.1210/jc.2007-2561 PubMed DOI

Parrish-Novak J, Dillon SR, Nelson A, Hammond A, Sprecher C, Gross JA, et al. Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function. Nature. (2000) 408:57–63. 10.1038/35040504 PubMed DOI

Pronk CJ, Veiby OP, Bryder D, Jacobsen SE. Tumor necrosis factor restricts hematopoietic stem cell activity in mice: involvement of two distinct receptors. J Exp Med. (2011) 208:1563–70. 10.1084/jem.20110752 PubMed DOI PMC

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) 30:1779–88. 10.1096/fj.201500175 PubMed DOI

Avecilla ST, Hattori K, Heissig B, Tejada R, Liao F, Shido K, et al. . Chemokine-mediated interaction of hematopoietic progenitors with the bone marrow vascular niche is required for thrombopoiesis. Nat Med. (2004) 10:64–71. 10.1038/nm973 PubMed DOI

Peled A, Kollet O, Ponomaryov T, Petit I, Franitza S, Grabovsky V, et al. . The chemokine SDF-1 activates the integrins LFA-1, VLA-4, and VLA-5 on immature human CD34(+) cells: role in transendothelial/stromal migration and engraftment of NOD/SCID mice. Blood. (2000) 95:3289–96. 10.1182/blood.V95.11.3289.011k33_3289_3296 PubMed DOI

Ferraro F, Lymperi S, Mendez-Ferrer S, Saez B, Spencer JA, Yeap BY, et al. . Diabetes impairs hematopoietic stem cell mobilization by altering niche function. Sci Transl Med. (2011) 3:104ra101. 10.1126/scitranslmed.3002191 PubMed DOI PMC

Chang E, Paterno J, Duscher D, Maan ZN, Chen JS, Januszyk M, et al. . Exercise induces stromal cell-derived factor-1alpha-mediated release of endothelial progenitor cells with increased vasculogenic function. Plast Reconstr Surg. (2015) 135:340–50e. 10.1097/PRS.0000000000000917 PubMed DOI PMC

Yoshihara H, Arai F, Hosokawa K, Hagiwara T, Takubo K, Nakamura Y, et al. . Thrombopoietin/MPL signaling regulates hematopoietic stem cell quiescence and interaction with the osteoblastic niche. Cell Stem Cell. (2007) 1:685–97. 10.1016/j.stem.2007.10.020 PubMed DOI

Nagahisa H, Nagata Y, Ohnuki T, Osada M, Nagasawa T, Abe T, et al. . Bone marrow stromal cells produce thrombopoietin and stimulate megakaryocyte growth and maturation but suppress proplatelet formation. Blood. (1996) 87:1309–16. 10.1182/blood.V87.4.1309.bloodjournal8741309 PubMed DOI

Kraakman MJ, Lee MK, Al-Sharea A, Dragoljevic D, Barrett TJ, Montenont E, et al. . Neutrophil-derived S100 calcium-binding proteins A8/A9 promote reticulated thrombocytosis and atherogenesis in diabetes. J Clin Invest. (2017) 127:2133–47. 10.1172/JCI92450 PubMed DOI PMC

Coban E, Yilmaz A, Sari R. The effect of weight loss on the mean platelet volume in obese patients. Platelets. (2007) 18:212–6. 10.1080/09537100600975362 PubMed DOI

Arai F, Hirao A, Ohmura M, Sato H, Matsuoka S, Takubo K, et al. . Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell. (2004) 118:149–61. 10.1016/j.cell.2004.07.004 PubMed DOI

Keats EC, Dominguez JM, II, Grant MB, Khan ZA. Switch from canonical to noncanonical Wnt signaling mediates high glucose-induced adipogenesis. Stem Cells. (2014) 32:1649–60. 10.1002/stem.1659 PubMed DOI PMC

Li Z, Hardij J, Evers SS, Hutch CR, Choi SM, Shao Y, et al. . G-CSF partially mediates effects of sleeve gastrectomy on the bone marrow niche. J Clin Invest. (2019) 129:2404–16. 10.1172/JCI126173 PubMed DOI PMC

Trottier MD, Naaz A, Li Y, Fraker PJ. Enhancement of hematopoiesis and lymphopoiesis in diet-induced obese mice. Proc Natl Acad Sci USA. (2012) 109:7622–9. 10.1073/pnas.1205129109 PubMed DOI PMC

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. (2013) 238:375–84. 10.1177/1535370213477976 PubMed DOI

Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature. (2003) 423:337–42. 10.1038/nature01658 PubMed DOI

Halade GV, El Jamali A, Williams PJ, Fajardo RJ, Fernandes G. Obesity-mediated inflammatory microenvironment stimulates osteoclastogenesis and bone loss in mice. Exp Gerontol. (2011) 46:43–52. 10.1016/j.exger.2010.09.014 PubMed DOI PMC

Kim JY, Kim HJ, Kim CS. Effects of 12-week combined exercise on RANKL/RANK/OPG signaling and bone-resorption cytokines in healthy college females. J Exerc Nutr Biochem. (2019) 23:13–20. 10.20463/jenb.2019.0003 PubMed DOI PMC

Costa A, Principi E, Lazzarini E, Descalzi F, Cancedda R, Castagnola P, et al. . LCN2 overexpression in bone enhances the hematopoietic compartment via modulation of the bone marrow microenvironment. J Cell Physiol. (2017) 232:3077–87. 10.1002/jcp.25755 PubMed DOI

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:e26241. 10.1371/journal.pone.0026241 PubMed DOI PMC

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) 9:841–8. 10.1089/152581600750062264 PubMed DOI

Qian H, Buza-Vidas N, Hyland CD, Jensen CT, Antonchuk J, Mansson R, et al. . Critical role of thrombopoietin in maintaining adult quiescent hematopoietic stem cells. Cell Stem Cell. (2007) 1:671–84. 10.1016/j.stem.2007.10.008 PubMed DOI

Petit A, Szyper-Kravitz M, Nagler A, Lahav M, Peled A, Habler L, et al. . G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and up-regulating CXCR4. Nat Immunol. (2002) 3:687–94. 10.1038/ni813 PubMed DOI

Peled A, Petit I, Kollet O, Magid M, Ponomaryov T, Byk T, et al. . Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4. Science. (1999) 283:845–8. 10.1126/science.283.5403.845 PubMed DOI

Taichman RS, Emerson SG. The role of osteoblasts in the hematopoietic microenvironment. Stem Cells. (1998) 16:7–15. 10.1002/stem.160007 PubMed DOI

Fulzele K, Krause DS, Panaroni C, Saini V, Barry KJ, Liu X, et al. . Myelopoiesis is regulated by osteocytes through Gsalpha-dependent signaling. Blood. (2013) 121:930–9. 10.1182/blood-2012-06-437160 PubMed DOI PMC

Weissman IL. Stem cells: units of development, units of regeneration, and units in evolution. Cell. (2000) 100:157–68. 10.1016/S0092-8674(00)81692-X PubMed DOI

Kondo M, Wagers AJ, Manz MG, Prohaska SS, Scherer DC, Beilhack GF, et al. . Biology of hematopoietic stem cells and progenitors: implications for clinical application. Annu Rev Immunol. (2003) 21:759–806. 10.1146/annurev.immunol.21.120601.141007 PubMed DOI

Bryder Rossi DJ, Weissman IL. Hematopoietic stem cells: the paradigmatic tissue-specific stem cell. Am J Pathol. (2006) 169:338–46. 10.2353/ajpath.2006.060312 PubMed DOI PMC

Kawamoto H, Katsura Y. A new paradigm for hematopoietic cell lineages: revision of the classical concept of the myeloid-lymphoid dichotomy. Trends Immunol. (2009) 30:193–200. 10.1016/j.it.2009.03.001 PubMed DOI

Ema H, Morita Y, Suda T. Heterogeneity and hierarchy of hematopoietic stem cells. Exp Hematol. (2014) 42:74–82 e2. 10.1016/j.exphem.2013.11.004 PubMed DOI

Ramalingam P, Poulos MG, Butler JM. Regulation of the hematopoietic stem cell lifecycle by the endothelial niche. Curr Opin Hematol. (2017) 24:289–99. 10.1097/MOH.0000000000000350 PubMed DOI PMC

Asada N, Kunisaki Y, Pierce H, Wang Z, Fernandez NF, Birbrair A, et al. . Differential cytokine contributions of perivascular haematopoietic stem cell niches. Nat Cell Biol. (2017) 19:214–23. 10.1038/ncb3475 PubMed DOI PMC

Zhao M, Perry JM, Marshall H, Venkatraman A, Qian P, He XC, et al. . Megakaryocytes maintain homeostatic quiescence and promote post-injury regeneration of hematopoietic stem cells. Nat Med. (2014) 20:1321–6. 10.1038/nm.3706 PubMed DOI

Winkler IG, Sims NA, Pettit AR, Barbier V, Nowlan B, Helwani F, et al. . Bone marrow macrophages maintain hematopoietic stem cell (HSC) niches and their depletion mobilizes HSCs. Blood. (2010) 116:4815–28. 10.1182/blood-2009-11-253534 PubMed DOI

Schofield R. The relationship between the spleen colony-forming cell and the haemopoietic stem cell. Blood Cells. (1978) 4:7–25. PubMed

Whitlock CA, Witte ON. Long-term culture of B lymphocytes and their precursors from murine bone marrow. Proc Natl Acad Sci USA. (1982) 79:3608–12. 10.1073/pnas.79.11.3608 PubMed DOI PMC

Whitlock CA, Tidmarsh GF, Muller-Sieburg C, Weissman IL. Bone marrow stromal cell lines with lymphopoietic activity express high levels of a pre-B neoplasia-associated molecule. Cell. (1987) 48:1009–21. 10.1016/0092-8674(87)90709-4 PubMed DOI

Nakano T, Kodama H, Honjo T. Generation of lymphohematopoietic cells from embryonic stem cells in culture. Science. (1994) 265:1098–101. 10.1126/science.8066449 PubMed DOI

Tikhonova AN, Dolgalev I, Hu H, Sivaraj KK, Hoxha E, Cuesta-Dominguez A, et al. . The bone marrow microenvironment at single-cell resolution. Nature. (2019) 569:222–8. 10.1038/s41586-019-1104-8 PubMed DOI PMC

Mirantes C, Passegue E, Pietras EM. Pro-inflammatory cytokines: emerging players regulating HSC function in normal and diseased hematopoiesis. Exp Cell Res. (2014) 329:248–54. 10.1016/j.yexcr.2014.08.017 PubMed DOI PMC

Battu S, Afroz S, Giddaluru J, Naz S, Huang W, Khumukcham SS, et al. . Amino acid starvation sensing dampens IL-1beta production by activating riboclustering and autophagy. PLoS Biol. (2018) 16:e2005317. 10.1371/journal.pbio.2005317 PubMed DOI PMC

Yamashita M, Passegue E. TNF-alpha coordinates hematopoietic stem cell survival and myeloid regeneration. Cell Stem Cell. (2019) 25:357–72 e7. 10.1016/j.stem.2019.05.019 PubMed DOI PMC

Ota K, Quint P, Ruan M, Pederson L, Westendorf JJ, Khosla S, et al. . TGF-beta induces Wnt10b in osteoclasts from female mice to enhance coupling to osteoblasts. Endocrinology. (2013) 154:3745–52. 10.1210/en.2013-1272 PubMed DOI PMC

Bennett CN, Longo KA, Wright WS, Suva LJ, Lane TF, Hankenson KD, et al. . Regulation of osteoblastogenesis and bone mass by Wnt10b. Proc Natl Acad Sci USA. (2005) 102:3324–9. 10.1073/pnas.0408742102 PubMed DOI PMC

Ota K, Quint P, Weivoda MM, Ruan M, Pederson L, Westendorf JJ, et al. . Transforming growth factor beta 1 induces CXCL16 and leukemia inhibitory factor expression in osteoclasts to modulate migration of osteoblast progenitors. Bone. (2013) 57:68–75. 10.1016/j.bone.2013.07.023 PubMed DOI PMC

Hayman AR. Tartrate-resistant acid phosphatase (TRAP) and the osteoclast/immune cell dichotomy. Autoimmunity. (2008) 41:218–23. 10.1080/08916930701694667 PubMed DOI

Lecka-Czernik B, Stechschulte LA, Czernik PJ, Dowling AR. High bone mass in adult mice with diet-induced obesity results from a combination of initial increase in bone mass followed by attenuation in bone formation; implications for high bone mass and decreased bone quality in obesity. Mol Cell Endocrinol. (2015) 410:35–41. 10.1016/j.mce.2015.01.001 PubMed DOI

McGrath C, Sankaran JS, Misaghian-Xanthos N, Sen B, Xie Z, Styner MA, et al. . Exercise degrades bone in caloric restriction, despite suppression of Marrow Adipose Tissue (MAT). J Bone Miner Res. (2019) 35:106–15. 10.1002/jbmr.3872 PubMed DOI PMC

Lotinun S, Kiviranta R, Matsubara T, Alzate JA, Neff L, Luth A, et al. . Osteoclast-specific cathepsin K deletion stimulates S1P-dependent bone formation. J Clin Invest. (2013) 123:666–81. 10.1172/JCI64840 PubMed DOI PMC

Kimura H, Kwan KM, Zhang Z, Deng JM, Darnay BG, Behringer RR, et al. . Cthrc1 is a positive regulator of osteoblastic bone formation. PLoS ONE. (2008) 3:e3174. 10.1371/journal.pone.0003174 PubMed DOI PMC

Mitroulis Chen LS, Singh RP, Kourtzelis I, Economopoulou M, Kajikawa T, et al. . Secreted protein Del-1 regulates myelopoiesis in the hematopoietic stem cell niche. J Clin Invest. (2017) 127:3624–39. 10.1172/JCI92571 PubMed DOI PMC

Nakamura-Ishizu Okuno Y, Omatsu Y, Okabe K, Morimoto J, Uede T, et al. . Extracellular matrix protein tenascin-C is required in the bone marrow microenvironment primed for hematopoietic regeneration. Blood. (2012) 119:5429–37. 10.1182/blood-2011-11-393645 PubMed DOI PMC

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. (2016) 24:2522–32. 10.1002/oby.21660 PubMed DOI

Singh P, Yao Y, Weliver A, Broxmeyer HE, Hong SC, Chang CH. Vaccinia virus infection modulates the hematopoietic cell compartments in the bone marrow. Stem Cells. (2008) 26:1009–16. 10.1634/stemcells.2007-0461 PubMed DOI PMC

Cheshier SH, Prohaska SS, Weissman IL. The effect of bleeding on hematopoietic stem cell cycling and self-renewal. Stem Cells Dev. (2007) 16:707–17. 10.1089/scd.2007.0017 PubMed DOI

Gueders MM, Hirst SJ, Quesada-Calvo F, Paulissen G, Hacha J, Gilles C, et al. . Matrix metalloproteinase-19 deficiency promotes tenascin-C accumulation and allergen-induced airway inflammation. Am J Respir Cell Mol Biol. (2010) 43:286–95. 10.1165/rcmb.2008-0426OC PubMed DOI

Klein G, Beck S, Muller CA. Tenascin is a cytoadhesive extracellular matrix component of the human hematopoietic microenvironment. J Cell Biol. (1993) 123:1027–35. 10.1083/jcb.123.4.1027 PubMed DOI PMC

Nagai Y, Garrett KP, Ohta S, Bahrun U, Kouro T, Akira S, et al. . Toll-like receptors on hematopoietic progenitor cells stimulate innate immune system replenishment. Immunity. (2006) 24:801–12. 10.1016/j.immuni.2006.04.008 PubMed DOI PMC

Baldridge MT, King KY, Goodell MA. Inflammatory signals regulate hematopoietic stem cells. Trends Immunol. (2011) 32:57–65. 10.1016/j.it.2010.12.003 PubMed DOI PMC

Baldridge MT, King KY, Boles NC, Weksberg DC, Goodell MA. Quiescent haematopoietic stem cells are activated by IFN-gamma in response to chronic infection. Nature. (2010) 465:793–7. 10.1038/nature09135 PubMed DOI PMC

King KY, Goodell MA. Inflammatory modulation of HSCs: viewing the HSC as a foundation for the immune response. Nat Rev Immunol. (2011) 11:685–92. 10.1038/nri3062 PubMed DOI PMC

Nicholson GC, Malakellis M, Collier FM, Cameron PU, Holloway WR, Gough TJ, et al. . Induction of osteoclasts from CD14-positive human peripheral blood mononuclear cells by receptor activator of nuclear factor kappaB ligand (RANKL). Clin Sci. (2000) 99:133–40. 10.1042/cs0990133 PubMed DOI

Suda T, Takahashi N, Udagawa N, Jimi E, Gillespie MT, Martin TJ. Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr Rev. (1999) 20:345–57. 10.1210/edrv.20.3.0367 PubMed DOI

Raisz LG. Physiology and pathophysiology of bone remodeling. Clin Chem. (1999) 45:1353–8. PubMed

Tang Y, Wu X, Lei W, Pang L, Wan C, Shi Z, et al. . TGF-beta1-induced migration of bone mesenchymal stem cells couples bone resorption with formation. Nat Med. (2009) 15:757–65. 10.1038/nm.1979 PubMed DOI PMC

Xian L, Wu X, Pang L, Lou M, Rosen CJ, Qiu T, et al. . Matrix IGF-1 maintains bone mass by activation of mTOR in mesenchymal stem cells. Nat Med. (2012) 18:1095–101. 10.1038/nm.2793 PubMed DOI PMC

Zenger S, Hollberg K, Ljusberg J, Norgard M, Ek-Rylander B, Kiviranta R, et al. . Proteolytic processing and polarized secretion of tartrate-resistant acid phosphatase is altered in a subpopulation of metaphyseal osteoclasts in cathepsin K-deficient mice. Bone. (2007) 41:820–32. 10.1016/j.bone.2007.07.010 PubMed DOI

Fuller K, Lawrence KM, Ross JL, Grabowska UB, Shiroo M, Samuelsson B, et al. . Cathepsin K inhibitors prevent matrix-derived growth factor degradation by human osteoclasts. Bone. (2008) 42:200–11. 10.1016/j.bone.2007.09.044 PubMed DOI

Takeshita S, Fumoto T, Matsuoka K, Park KA, Aburatani H, Kato S, et al. . Osteoclast-secreted CTHRC1 in the coupling of bone resorption to formation. J Clin Invest. (2013) 123:3914–24. 10.1172/JCI69493 PubMed DOI PMC

Rao GM, Morghom LO. Effect of obesity on erythrocyte count and hemoglobin levels in Libyan diabetic patients. Clin Physiol Biochem. (1986) 4:277–80. PubMed

Mairbaurl H. Red blood cells in sports: effects of exercise and training on oxygen supply by red blood cells. Front Physiol. (2013) 4:332. 10.3389/fphys.2013.00332 PubMed DOI PMC

Collins N, Han SJ, Enamorado M, Link VM, Huang B, Moseman EA, et al. . The bone marrow protects and optimizes immunological memory during dietary restriction. Cell. (2019) 178:1088–101 e15. 10.1016/j.cell.2019.07.049 PubMed DOI PMC

Romashkan SV, Das SK, Villareal DT, Ravussin E, Redman LM, Rochon J, et al. . Safety of two-year caloric restriction in non-obese healthy individuals. Oncotarget. (2016) 7:19124–33. 10.18632/oncotarget.8093 PubMed DOI PMC

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) 26:4855–63. 10.1096/fj.12-209841 PubMed DOI PMC

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. (2017) 25:1745–53. 10.1002/oby.21958 PubMed DOI PMC

Nagareddy PR, Kraakman M, Masters SL, Stirzaker RA, Gorman DJ, Grant RW, et al. . Adipose tissue macrophages promote myelopoiesis and monocytosis in obesity. Cell Metab. (2014) 19:821–35. 10.1016/j.cmet.2014.03.029 PubMed DOI PMC

Nagareddy PR, Murphy AJ, Stirzaker RA, Hu Y, Yu S, Miller RG, et al. . Hyperglycemia promotes myelopoiesis and impairs the resolution of atherosclerosis. Cell Metab. (2013) 17:695–708. 10.1016/j.cmet.2013.04.001 PubMed DOI PMC

Shu L, Beier E, Sheu T, Zhang H, Zuscik MJ, Puzas EJ, et al. . High-fat diet causes bone loss in young mice by promoting osteoclastogenesis through alteration of the bone marrow environment. Calcif Tissue Int. (2015) 96:313–23. 10.1007/s00223-015-9954-z PubMed DOI PMC

Gerbaix M, Metz L, Mac-Way F, Lavet C, Guillet C, Walrand S, et al. . A well-balanced diet combined or not with exercise induces fat mass loss without any decrease of bone mass despite bone micro-architecture alterations in obese rat. Bone. (2013) 53:382–90. 10.1016/j.bone.2013.01.006 PubMed DOI

Calixto MC, Lintomen L, Schenka A, Saad MJ, Zanesco A, Antunes E. Obesity enhances eosinophilic inflammation in a murine model of allergic asthma. Br J Pharmacol. (2010) 159:617–25. 10.1111/j.1476-5381.2009.00560.x PubMed DOI PMC

Bolus WR, Kennedy AJ, Hasty AH. Obesity-induced reduction of adipose eosinophils is reversed with low-calorie dietary intervention. Physiol Rep. (2018) 6:e13919. 10.14814/phy2.13919 PubMed DOI PMC

Schwartz C, Eberle JU, Voehringer D. Basophils in inflammation. Eur J Pharmacol. (2016) 778:90–5. 10.1016/j.ejphar.2015.04.049 PubMed DOI

Howarth PH, Pao GJ, Church MK, Holgate ST. Exercise and isocapnic hyperventilation-induced bronchoconstriction in asthma: relevance of circulating basophils to measurements of plasma histamine. J Allergy Clin Immunol. (1984) 73:391–9. 10.1016/0091-6749(84)90414-7 PubMed DOI

Brotfain E, Hadad N, Shapira Y, Avinoah E, Zlotnik A, Raichel L, et al. . Neutrophil functions in morbidly obese subjects. Clin Exp Immunol. (2015) 181:156–63. 10.1111/cei.12631 PubMed DOI PMC

Kawanishi N, Niihara H, Mizokami T, Yada K, Suzuki K. Exercise training attenuates neutrophil infiltration and elastase expression in adipose tissue of high-fat-diet-induced obese mice. Physiol Rep. (2015) 3:e12534. 10.14814/phy2.12534 PubMed DOI PMC

Imayama I, Ulrich CM, Alfano CM, Wang C, Xiao L, Wener MH, et a;. Effects of a caloric restriction weight loss diet and exercise on inflammatory biomarkers in overweight/obese postmenopausal women: a randomized controlled trial. Cancer Res. (2012) 72:2314–26. 10.1158/0008-5472.CAN-11-3092 PubMed DOI PMC

Collins AT, Kulvaranon ML, Cutcliffe HC, Utturkar GM, Smith WAR, Spritzer CE, et al. . Obesity alters the in vivo mechanical response and biochemical properties of cartilage as measured by MRI. Arthritis Res Ther. (2018) 20:232. 10.1186/s13075-018-1727-4 PubMed DOI PMC

Ruiz M, Maumus M, Fonteneau G, Pers YM, Ferreira R, Dagneaux L, et al. . TGFbetai is involved in the chondrogenic differentiation of mesenchymal stem cells and is dysregulated in osteoarthritis. Osteoarthritis Cartilage. (2019) 27:493–503. 10.1016/j.joca.2018.11.005 PubMed DOI

Yamaguchi S, Aoyama T, Ito A, Nagai M, Iijima H, Tajino J, et al. . The effect of exercise on the early stages of mesenchymal stromal cell-induced cartilage repair in a rat osteochondral defect model. PLoS ONE. (2016) 11:e0151580. 10.1371/journal.pone.0151580 PubMed DOI PMC

Fontinele RG, Krause Neto W, Gama EF, Brito Mari R, de Souza RR, Conrado A, et al. . Caloric restriction minimizes aging effects on the femoral medial condyle. Aging Male. (2017) 20:161–7. 10.1080/13685538.2017.1301418 PubMed DOI

Watkins BA, Li Y, Lippman HE, Feng S. Modulatory effect of omega-3 polyunsaturated fatty acids on osteoblast function and bone metabolism. Prostaglandins Leukot Essent Fatty Acids. (2003) 68:387–98. 10.1016/S0952-3278(03)00063-2 PubMed DOI

Sun D, Krishnan A, Zaman K, Lawrence R, Bhattacharya A, Fernandes G. Dietary n-3 fatty acids decrease osteoclastogenesis and loss of bone mass in ovariectomized mice. J Bone Miner Res. (2003) 18:1206–16. 10.1359/jbmr.2003.18.7.1206 PubMed DOI

Inzana JA, Kung M, Shu L, Hamada D, Xing LP, Zuscik MJ, et al. . Immature mice are more susceptible to the detrimental effects of high fat diet on cancellous bone in the distal femur. Bone. (2013) 57:174–83. 10.1016/j.bone.2013.08.003 PubMed DOI PMC

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. (2016) 7:102. 10.3389/fendo.2016.00102 PubMed DOI PMC

Tie G, Messina KE, Yan J, Messina JA, Messina LM. Hypercholesterolemia induces oxidant stress that accelerates the ageing of hematopoietic stem cells. J Am Heart Assoc. (2014) 3:e000241. 10.1161/JAHA.113.000241 PubMed DOI PMC

Luo Y, Chen GL, Hannemann N, Ipseiz N, Kronke G, Bauerle T, et al. . Microbiota from obese mice regulate hematopoietic stem cell differentiation by altering the bone niche. Cell Metab. (2015) 22:886–94. 10.1016/j.cmet.2015.08.020 PubMed DOI

Bolus WR, Peterson KR, Hubler MJ, Kennedy AJ, Gruen ML, Hasty AH. Elevating adipose eosinophils in obese mice to physiologically normal levels does not rescue metabolic impairments. Mol Metab. (2018) 8:86–95. 10.1016/j.molmet.2017.12.004 PubMed DOI PMC

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) 20:771–84 e6. 10.1016/j.stem.2017.02.009 PubMed DOI PMC

Cortez M, Carmo LS, Rogero MM, Borelli P, Fock RA. A high-fat diet increases IL-1, IL-6, and TNF-alpha production by increasing NF-kappaB and attenuating PPAR-gamma expression in bone marrow mesenchymal stem cells. Inflammation. (2013) 36:379–86. 10.1007/s10753-012-9557-z PubMed DOI

Tencerova M, Frost M, Figeac F, Nielsen TK, Ali D, Lauterlein JL, et al. . Obesity-associated hypermetabolism and accelerated senescence of bone marrow stromal stem cells suggest a potential mechanism for bone fragility. Cell Rep. (2019) 27:2050–62 e6. 10.1016/j.celrep.2019.04.066 PubMed DOI

Xu F, Du Y, Hang S, Chen A, Guo F, Xu T. Adipocytes regulate the bone marrow microenvironment in a mouse model of obesity. Mol Med Rep. (2013) 8:823–8. 10.3892/mmr.2013.1572 PubMed DOI

Wu D, Ren Z, Pae M, Guo W, Cui X, Merrill AH, et al. . Aging up-regulates expression of inflammatory mediators in mouse adipose tissue. J Immunol. (2007) 179:4829–39. 10.4049/jimmunol.179.7.4829 PubMed DOI

Naranjo MC, Garcia I, Bermudez B, Lopez S, Cardelo MP, Abia R, et al. . Acute effects of dietary fatty acids on osteclastogenesis via RANKL/RANK/OPG system. Mol Nutr Food Res. (2016) 60:2505–13. 10.1002/mnfr.201600303 PubMed DOI

Cao JJ, Gregoire BR, Michelsen KG, Picklo MJ. Increasing dietary fish oil reduces adiposity and mitigates bone deterioration in growing C57BL/6 mice fed a high-fat diet. J Nutr. (2019) 150:99–107. 10.1093/jn/nxz215 PubMed DOI

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. 10.1002/jbmr.3159 PubMed DOI PMC

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) 27:747–56. 10.1007/s00198-015-3289-5 PubMed DOI

Baker JM, De Lisio M, Parise G. Endurance exercise training promotes medullary hematopoiesis. FASEB J. (2011) 25:4348–57. 10.1096/fj.11-189043 PubMed DOI

De Lisio M, Parise G. Characterization of the effects of exercise training on hematopoietic stem cell quantity and function. J Appl Physiol. (2012) 113:1576–84. 10.1152/japplphysiol.00717.2012 PubMed DOI PMC

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

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) 25:2078–88. 10.1002/jbmr.82 PubMed DOI PMC

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) 157:508–21. 10.1210/en.2015-1477 PubMed DOI PMC

Bredella MA, Fazeli PK, Miller KK, Misra M, Torriani M, Thomas BJ, et al. . Increased bone marrow fat in anorexia nervosa. J Clin Endocrinol Metab. (2009) 94:2129–36. 10.1210/jc.2008-2532 PubMed DOI PMC

Han J, Luo T, Gu Y, Li G, Jia W, Luo M. Cathepsin K regulates adipocyte differentiation: possible involvement of type I collagen degradation. Endocr J. (2009) 56:55–63. 10.1507/endocrj.K08E-143 PubMed DOI

Stohn JP, Wang Q, Siviski ME, Kennedy K, Jin YR, Kacer D, et al. . Cthrc1 controls adipose tissue formation, body composition, and physical activity. Obesity. (2015) 23:1633–42. 10.1002/oby.21144 PubMed DOI PMC

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

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