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

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, hig...

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Autores principales: Ambrosi, Thomas H., Scialdone, Antonio, Graja, Antonia, Gohlke, Sabrina, Jank, Anne-Marie, Bocian, Carla, Woelk, Lena, Fan, Hua, Logan, Darren W., Schürmann, Annette, Saraiva, Luis R., Schulz, Tim J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5459794/
https://www.ncbi.nlm.nih.gov/pubmed/28330582
http://dx.doi.org/10.1016/j.stem.2017.02.009
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author Ambrosi, Thomas H.
Scialdone, Antonio
Graja, Antonia
Gohlke, Sabrina
Jank, Anne-Marie
Bocian, Carla
Woelk, Lena
Fan, Hua
Logan, Darren W.
Schürmann, Annette
Saraiva, Luis R.
Schulz, Tim J.
author_facet Ambrosi, Thomas H.
Scialdone, Antonio
Graja, Antonia
Gohlke, Sabrina
Jank, Anne-Marie
Bocian, Carla
Woelk, Lena
Fan, Hua
Logan, Darren W.
Schürmann, Annette
Saraiva, Luis R.
Schulz, Tim J.
author_sort Ambrosi, Thomas H.
collection PubMed
description 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.
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spelling pubmed-54597942017-06-14 Adipocyte Accumulation in the Bone Marrow during Obesity and Aging Impairs Stem Cell-Based Hematopoietic and Bone Regeneration Ambrosi, Thomas H. Scialdone, Antonio Graja, Antonia Gohlke, Sabrina Jank, Anne-Marie Bocian, Carla Woelk, Lena Fan, Hua Logan, Darren W. Schürmann, Annette Saraiva, Luis R. Schulz, Tim J. Cell Stem Cell Article 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. Cell Press 2017-06-01 /pmc/articles/PMC5459794/ /pubmed/28330582 http://dx.doi.org/10.1016/j.stem.2017.02.009 Text en © 2017 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Ambrosi, Thomas H.
Scialdone, Antonio
Graja, Antonia
Gohlke, Sabrina
Jank, Anne-Marie
Bocian, Carla
Woelk, Lena
Fan, Hua
Logan, Darren W.
Schürmann, Annette
Saraiva, Luis R.
Schulz, Tim J.
Adipocyte Accumulation in the Bone Marrow during Obesity and Aging Impairs Stem Cell-Based Hematopoietic and Bone Regeneration
title Adipocyte Accumulation in the Bone Marrow during Obesity and Aging Impairs Stem Cell-Based Hematopoietic and Bone Regeneration
title_full Adipocyte Accumulation in the Bone Marrow during Obesity and Aging Impairs Stem Cell-Based Hematopoietic and Bone Regeneration
title_fullStr Adipocyte Accumulation in the Bone Marrow during Obesity and Aging Impairs Stem Cell-Based Hematopoietic and Bone Regeneration
title_full_unstemmed Adipocyte Accumulation in the Bone Marrow during Obesity and Aging Impairs Stem Cell-Based Hematopoietic and Bone Regeneration
title_short Adipocyte Accumulation in the Bone Marrow during Obesity and Aging Impairs Stem Cell-Based Hematopoietic and Bone Regeneration
title_sort adipocyte accumulation in the bone marrow during obesity and aging impairs stem cell-based hematopoietic and bone regeneration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5459794/
https://www.ncbi.nlm.nih.gov/pubmed/28330582
http://dx.doi.org/10.1016/j.stem.2017.02.009
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