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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2014
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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. |
format | Online Article Text |
id | pubmed-4429037 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
record_format | MEDLINE/PubMed |
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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