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B Cell Production of Both OPG and RANKL is Significantly Increased in Aged Mice

Aging is a risk factor for osteoclastic bone loss and bone fracture. Receptor activator of NF-κB ligand (RANKL) is the key effector cytokine for osteoclastogenesis and bone resorption, and is moderated by its decoy receptor osteoprotegerin (OPG). The development of an inflammatory environment during...

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Autores principales: Li, Yan, Terauchi, Masakazu, Vikulina, Tatyana, Roser-Page, Susanne, Weitzmann, M. N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4429037/
https://www.ncbi.nlm.nih.gov/pubmed/25984250
http://dx.doi.org/10.2174/1876525401406010008
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author Li, Yan
Terauchi, Masakazu
Vikulina, Tatyana
Roser-Page, Susanne
Weitzmann, M. N.
author_facet Li, Yan
Terauchi, Masakazu
Vikulina, Tatyana
Roser-Page, Susanne
Weitzmann, M. N.
author_sort Li, Yan
collection PubMed
description Aging is a risk factor for osteoclastic bone loss and bone fracture. Receptor activator of NF-κB ligand (RANKL) is the key effector cytokine for osteoclastogenesis and bone resorption, and is moderated by its decoy receptor osteoprotegerin (OPG). The development of an inflammatory environment during aging leads to increased bone resorption and loss of bone mineral density (BMD). Interestingly, animal and clinical studies show that OPG is actually increased in aging but fails to fully compensate for endogenous RANKL. Osteoblast- and B-lineage cells are significant sources of physiological OPG, however osteoblast OPG production declines with age, suggesting that elevated OPG in aging may be a consequence of changes in B cell function. In this study we examined BMD and indices of trabecular bone structure during aging, and B cell production of both RANKL and OPG in young and aged mice. Our data reveal significant loss of BMD and trabecular structure with age commensurate with significantly elevated concentrations of both OPG and RANKL in aged mice, and a decline in B cell populations in aged animals. Taken together our data suggest that B cells may be responsible for the elevated concentrations of OPG during aging and are essential to counteract excessive age-associated bone resorption. Paradoxically, B cells themselves likely contribute RANKL in aging and the loss of B cells with age may further contribute to the imbalance in OPG relative to RANKL that predisposes age-associated bone loss.
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spelling pubmed-44290372015-05-13 B Cell Production of Both OPG and RANKL is Significantly Increased in Aged Mice Li, Yan Terauchi, Masakazu Vikulina, Tatyana Roser-Page, Susanne Weitzmann, M. N. Open Bone J Article Aging is a risk factor for osteoclastic bone loss and bone fracture. Receptor activator of NF-κB ligand (RANKL) is the key effector cytokine for osteoclastogenesis and bone resorption, and is moderated by its decoy receptor osteoprotegerin (OPG). The development of an inflammatory environment during aging leads to increased bone resorption and loss of bone mineral density (BMD). Interestingly, animal and clinical studies show that OPG is actually increased in aging but fails to fully compensate for endogenous RANKL. Osteoblast- and B-lineage cells are significant sources of physiological OPG, however osteoblast OPG production declines with age, suggesting that elevated OPG in aging may be a consequence of changes in B cell function. In this study we examined BMD and indices of trabecular bone structure during aging, and B cell production of both RANKL and OPG in young and aged mice. Our data reveal significant loss of BMD and trabecular structure with age commensurate with significantly elevated concentrations of both OPG and RANKL in aged mice, and a decline in B cell populations in aged animals. Taken together our data suggest that B cells may be responsible for the elevated concentrations of OPG during aging and are essential to counteract excessive age-associated bone resorption. Paradoxically, B cells themselves likely contribute RANKL in aging and the loss of B cells with age may further contribute to the imbalance in OPG relative to RANKL that predisposes age-associated bone loss. 2014 /pmc/articles/PMC4429037/ /pubmed/25984250 http://dx.doi.org/10.2174/1876525401406010008 Text en © Li et al.; Licensee Bentham Open. This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.
spellingShingle Article
Li, Yan
Terauchi, Masakazu
Vikulina, Tatyana
Roser-Page, Susanne
Weitzmann, M. N.
B Cell Production of Both OPG and RANKL is Significantly Increased in Aged Mice
title B Cell Production of Both OPG and RANKL is Significantly Increased in Aged Mice
title_full B Cell Production of Both OPG and RANKL is Significantly Increased in Aged Mice
title_fullStr B Cell Production of Both OPG and RANKL is Significantly Increased in Aged Mice
title_full_unstemmed B Cell Production of Both OPG and RANKL is Significantly Increased in Aged Mice
title_short B Cell Production of Both OPG and RANKL is Significantly Increased in Aged Mice
title_sort b cell production of both opg and rankl is significantly increased in aged mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4429037/
https://www.ncbi.nlm.nih.gov/pubmed/25984250
http://dx.doi.org/10.2174/1876525401406010008
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