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The role of the P2X7 receptor on bone loss in a mouse model of inflammation-mediated osteoporosis

In inflammatory autoimmune diseases, bone loss is frequent. In most cases, secondary osteoporosis is caused by treatment with systemic glucocorticoid. However, the pathogenesis behind the bone loss is presumed multifactorial. We aimed to elucidate the role of the P2X7 receptor on bone mineral densit...

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Autores principales: Kvist, T.M., Syberg, S., Petersen, S., Ding, M., Jørgensen, N.R., Schwarz, P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5736855/
https://www.ncbi.nlm.nih.gov/pubmed/29276731
http://dx.doi.org/10.1016/j.bonr.2015.09.003
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author Kvist, T.M.
Syberg, S.
Petersen, S.
Ding, M.
Jørgensen, N.R.
Schwarz, P.
author_facet Kvist, T.M.
Syberg, S.
Petersen, S.
Ding, M.
Jørgensen, N.R.
Schwarz, P.
author_sort Kvist, T.M.
collection PubMed
description In inflammatory autoimmune diseases, bone loss is frequent. In most cases, secondary osteoporosis is caused by treatment with systemic glucocorticoid. However, the pathogenesis behind the bone loss is presumed multifactorial. We aimed to elucidate the role of the P2X7 receptor on bone mineral density (BMD), microarchitecture, and bone strength in a standardized mouse model of inflammation-mediated osteoporosis (IMO). In total 146 mice completed our protocol, 70 wild type (WT) mice and 76 P2X7 −/− (knockout, KO). BMD at the femur and spine decreased significantly from baseline to day 20 in the WT IMO mice (p < 0.01). In the WT vehicle, KO vehicle and KO IMO, no significant BMD changes were found. Bone strength showed a lower mid-shaft max strength (p = 0.038) and also a non-significant trend towards lower strength at the femoral neck of the WT IMO group. Trabecular bone volume fraction (BV/TV) and connectivity density (CD) after 20 days were significantly decreased in the WT IMO group (p = 0.001). In contrast, the WT vehicle and KO vehicle, BV/TV and CD did no change at 20 days. Cortical bone revealed no significant microarchitectural changes after 20 days in the WT IMO group, whereas the total cortical area increased significantly in WT vehicle and KO IMO after 20 days (5.2% and 8.8%, respectively). In conclusion, the P2X7 receptor KO mice did not respond to inflammation with loss of BMD whereas the WT mice had a significant loss of BMD, bone strength and trabecular microarchitecture, demonstrating a role for the P2X7 receptor in inflammatory bone loss.
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spelling pubmed-57368552017-12-22 The role of the P2X7 receptor on bone loss in a mouse model of inflammation-mediated osteoporosis Kvist, T.M. Syberg, S. Petersen, S. Ding, M. Jørgensen, N.R. Schwarz, P. Bone Rep Article In inflammatory autoimmune diseases, bone loss is frequent. In most cases, secondary osteoporosis is caused by treatment with systemic glucocorticoid. However, the pathogenesis behind the bone loss is presumed multifactorial. We aimed to elucidate the role of the P2X7 receptor on bone mineral density (BMD), microarchitecture, and bone strength in a standardized mouse model of inflammation-mediated osteoporosis (IMO). In total 146 mice completed our protocol, 70 wild type (WT) mice and 76 P2X7 −/− (knockout, KO). BMD at the femur and spine decreased significantly from baseline to day 20 in the WT IMO mice (p < 0.01). In the WT vehicle, KO vehicle and KO IMO, no significant BMD changes were found. Bone strength showed a lower mid-shaft max strength (p = 0.038) and also a non-significant trend towards lower strength at the femoral neck of the WT IMO group. Trabecular bone volume fraction (BV/TV) and connectivity density (CD) after 20 days were significantly decreased in the WT IMO group (p = 0.001). In contrast, the WT vehicle and KO vehicle, BV/TV and CD did no change at 20 days. Cortical bone revealed no significant microarchitectural changes after 20 days in the WT IMO group, whereas the total cortical area increased significantly in WT vehicle and KO IMO after 20 days (5.2% and 8.8%, respectively). In conclusion, the P2X7 receptor KO mice did not respond to inflammation with loss of BMD whereas the WT mice had a significant loss of BMD, bone strength and trabecular microarchitecture, demonstrating a role for the P2X7 receptor in inflammatory bone loss. Elsevier 2015-10-23 /pmc/articles/PMC5736855/ /pubmed/29276731 http://dx.doi.org/10.1016/j.bonr.2015.09.003 Text en © 2016 Published by Elsevier Inc. 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
Kvist, T.M.
Syberg, S.
Petersen, S.
Ding, M.
Jørgensen, N.R.
Schwarz, P.
The role of the P2X7 receptor on bone loss in a mouse model of inflammation-mediated osteoporosis
title The role of the P2X7 receptor on bone loss in a mouse model of inflammation-mediated osteoporosis
title_full The role of the P2X7 receptor on bone loss in a mouse model of inflammation-mediated osteoporosis
title_fullStr The role of the P2X7 receptor on bone loss in a mouse model of inflammation-mediated osteoporosis
title_full_unstemmed The role of the P2X7 receptor on bone loss in a mouse model of inflammation-mediated osteoporosis
title_short The role of the P2X7 receptor on bone loss in a mouse model of inflammation-mediated osteoporosis
title_sort role of the p2x7 receptor on bone loss in a mouse model of inflammation-mediated osteoporosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5736855/
https://www.ncbi.nlm.nih.gov/pubmed/29276731
http://dx.doi.org/10.1016/j.bonr.2015.09.003
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