Adipocyte Accumulation in the Bone Marrow during Obesity and Aging Impairs Stem Cell-Based Hematopoietic and Bone Regeneration

被引：745

作者：

Ambrosi, Thomas H. ^{[1
]}

Scialdone, Antonio ^{[2
,3
]}

Graja, Antonia ^{[1
]}

Gohlke, Sabrina ^{[1
]}

Jank, Anne-Marie ^{[1
]}

Bocian, Carla ^{[1
]}

Woelk, Lena ^{[1
]}

Fan, Hua ^{[4
]}

Logan, Darren W. ^{[2
,5
]}

Schuermann, Annette ^{[1
]}

Saraiva, Luis R. ^{[6
]}

Schulz, Tim J. ^{[1
,7
]}

机构：

[1] German Inst Human Nutr Potsdam Rehbrucke, D-14558 Nuthetal, Germany

[2] Wellcome Trust Sanger Inst, Wellcome Genome Campus, Hinxton Cambridge CB10 1SA, England

[3] European Mol Biol Lab, EMBL EBI, Wellcome Genome Campus, Hinxton Cambridge CB10 1SD, England

[4] Charite, D-10117 Berlin, Germany

[5] Monell Chem Senses Ctr, Philadelphia, PA 19104 USA

[6] Qatar Fdn, Sidra Med & Res Ctr, POB 26999, Doha, Qatar

[7] German Ctr Diabet Res DZD, D-85764 Munich, Germany

来源：

CELL STEM CELL | 2017年 / 20卷 / 06期

基金：

欧洲研究理事会;

关键词：

MESENCHYMAL STROMAL CELLS; DIPEPTIDYL-PEPTIDASE; 4; ADIPOSE-TISSUE; FAT; IDENTIFICATION; PROGENITORS; BROWN; ADIPOGENESIS; OSTEOGENESIS; EXPRESSION;

D O I：

10.1016/j.stem.2017.02.009

中图分类号：

Q813 [细胞工程];

学科分类号：

100113 [医学细胞生物学];

摘要：

Aging and obesity induce ectopic adipocyte accumulation in bone marrow cavities. This process is thought to impair osteogenic and hematopoietic regeneration. Here we specify the cellular identities of the adipogenic and osteogenic lineages of the bone. While aging impairs the osteogenic lineage, high-fat diet feeding activates expansion of the adipogenic lineage, an effect that is significantly enhanced in aged animals. We further describe a mesenchymal sub-population with stem cell-like characteristics that gives rise to both lineages and, at the same time, acts as a principal component of the hematopoietic niche by promoting competitive repopulation following lethal irradiation. Conversely, bone-resident cells committed to the adipocytic lineage inhibit hematopoiesis and bone healing, potentially by producing excessive amounts of Dipeptidyl peptidase-4, a protease that is a target of diabetes therapies. These studies delineate the molecular identity of the bone-resident adipocytic lineage, and they establish its involvement in age-dependent dysfunction of bone and hematopoietic regeneration.

引用

页码：771 / +

页数：20

共 52 条

[1]

Dipeptidyl-peptidase 4 Inhibition: Linking Metabolic Control to Cardiovascular Protection [J].

Avogaro, Angelo ;

de Kreutzenberg, Saula ;

Fadini, Gianpaolo .

CURRENT PHARMACEUTICAL DESIGN, 2014, 20 (14) :2387-2394

[2]

Berry Ryan, 2015, Curr Mol Biol Rep, V1, P101

[3]

Characterization of the adipocyte cellular lineage in vivo [J].

Berry, Ryan ;

Rodeheffer, Matthew S. .

NATURE CELL BIOLOGY, 2013, 15 (03) :302-308

[4]

Dipeptidylpeptidase 4 negatively regulates colony-stimulating factor activity and stress hematopoiesis [J].

Broxmeyer, Hal E. ;

Hoggatt, Jonathan ;

O'Leary, Heather A. ;

Mantel, Charlie ;

Chitteti, Brahmananda R. ;

Cooper, Scott ;

Messina-Graham, Steven ;

Hangoc, Giao ;

Farag, Sherif ;

Rohrabaugh, Sara L. ;

Ou, Xuan ;

Speth, Jennifer ;

Pelus, Louis M. ;

Srour, Edward F. ;

Campbell, Timothy B. .

NATURE MEDICINE, 2012, 18 (12) :1786-+

[5]

Bone damage in type 2 diabetes mellitus [J].

Carnevale, V. ;

Romagnoli, E. ;

D'Erasmo, L. ;

D'Erasmo, E. .

NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES, 2014, 24 (11) :1151-1157

[6]

Bone Marrow Adipose Tissue Is an Endocrine Organ that Contributes to Increased Circulating Adiponectin during Caloric Restriction [J].

Cawthorn, William P. ;

Scheller, Erica L. ;

Learman, Brian S. ;

Parlee, Sebastian D. ;

Simon, Becky R. ;

Mori, Hiroyuki ;

Ning, Xiaomin ;

Bree, Adam J. ;

Schell, Benjamin ;

Broome, David T. ;

Soliman, Sandra S. ;

DelProposto, Jenifer L. ;

Lumeng, Carey N. ;

Mitra, Aditi ;

Pandit, Sandeep V. ;

Gallagher, Katherine A. ;

Miller, Joshua D. ;

Krishnan, Venkatesh ;

Hui, Susanta K. ;

Bredella, Miriam A. ;

Fazeli, Pouneh K. ;

Klibanski, Anne ;

Horowitz, Mark C. ;

Rosen, Clifford J. ;

MacDougald, Ormond A. .

CELL METABOLISM, 2014, 20 (02) :368-375

[7]

Identification and Specification of the Mouse Skeletal Stem Cell [J].

Chan, Charles K. F. ;

Seo, Eun Young ;

Chen, James Y. ;

Lo, David ;

McArdle, Adrian ;

Sinha, Rahul ;

Tevlin, Ruth ;

Seita, Jun ;

Vincent-Tompkins, Justin ;

Wearda, Taylor ;

Lu, Wan-Jin ;

Senarath-Yapa, Kshemendra ;

Chung, Michael T. ;

Marecic, Owen ;

Tran, Misha ;

Yan, Kelley S. ;

Upton, Rosalynd ;

Walmsley, Graham G. ;

Lee, Andrew S. ;

Sahoo, Debashis ;

Kuo, Calvin J. ;

Weissman, Irving L. ;

Longaker, Michael T. .

CELL, 2015, 160 (1-2) :285-298

[8]

The bone-fat interface: basic and clinical implications of marrow adiposity [J].

Devlin, Maureen J. ;

Rosen, Clifford J. .

LANCET DIABETES & ENDOCRINOLOGY, 2015, 3 (02) :141-147

[9]

Endothelial and perivascular cells maintain haematopoietic stem cells [J].

Ding, Lei ;

Saunders, Thomas L. ;

Enikolopov, Grigori ;

Morrison, Sean J. .

NATURE, 2012, 481 (7382) :457-U65

[10]

A High Fat Diet Increases Bone Marrow Adipose Tissue (MAT) But Does Not Alter Trabecular or Cortical Bone Mass in C57BL/6J Mice [J].

Doucette, Casey R. ;

Horowitz, Mark C. ;

Berry, Ryan ;

MacDougald, Ormond A. ;

Anunciado-Koza, Rea ;

Koza, Robert A. ;

Rosen, Clifford J. .

JOURNAL OF CELLULAR PHYSIOLOGY, 2015, 230 (09) :2032-2037

← 1 2 3 4 5 6 →