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Bone Marrow Derived Extracellular Vesicles Activate Osteoclast Differentiation in Traumatic Brain Injury Induced Bone Loss
Traumatic brain injury (TBI) is a major source of worldwide morbidity and mortality. Patients suffering from TBI exhibit a higher susceptibility to bone loss and an increased rate of bone fractures; however, the underlying mechanisms remain poorly defined. Herein, we observed significantly lower bon...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356398/ https://www.ncbi.nlm.nih.gov/pubmed/30658394 http://dx.doi.org/10.3390/cells8010063 |
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author | Singleton, Quante Vaibhav, Kumar Braun, Molly Patel, Chandani Khayrullin, Andrew Mendhe, Bharati Lee, Byung R. Kolhe, Ravindra Kaiser, Helen Awad, Mohamed E. Fariyike, Tunde Elsayed, Ranya Elsalanty, Mohammed Isales, Carlos M. Liu, Yutao Hamrick, Mark W. Dhandapani, Krishnan M. Fulzele, Sadanand |
author_facet | Singleton, Quante Vaibhav, Kumar Braun, Molly Patel, Chandani Khayrullin, Andrew Mendhe, Bharati Lee, Byung R. Kolhe, Ravindra Kaiser, Helen Awad, Mohamed E. Fariyike, Tunde Elsayed, Ranya Elsalanty, Mohammed Isales, Carlos M. Liu, Yutao Hamrick, Mark W. Dhandapani, Krishnan M. Fulzele, Sadanand |
author_sort | Singleton, Quante |
collection | PubMed |
description | Traumatic brain injury (TBI) is a major source of worldwide morbidity and mortality. Patients suffering from TBI exhibit a higher susceptibility to bone loss and an increased rate of bone fractures; however, the underlying mechanisms remain poorly defined. Herein, we observed significantly lower bone quality and elevated levels of inflammation in bone and bone marrow niche after controlled cortical impact-induced TBI in in vivo CD-1 mice. Further, we identified dysregulated NF-κB signaling, an established mediator of osteoclast differentiation and bone loss, within the bone marrow niche of TBI mice. Ex vivo studies revealed increased osteoclast differentiation in bone marrow-derived cells from TBI mice, as compared to sham injured mice. We also found bone marrow derived extracellular vesicles (EVs) from TBI mice enhanced the colony forming ability and osteoclast differentiation efficacy and activated NF-κB signaling genes in bone marrow-derived cells. Additionally, we showed that miRNA-1224 up-regulated in bone marrow-derived EVs cargo of TBI. Taken together, we provide evidence that TBI-induced inflammatory stress on bone and the bone marrow niche may activate NF-κB leading to accelerated bone loss. Targeted inhibition of these signaling pathways may reverse TBI-induced bone loss and reduce fracture rates. |
format | Online Article Text |
id | pubmed-6356398 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-63563982019-02-06 Bone Marrow Derived Extracellular Vesicles Activate Osteoclast Differentiation in Traumatic Brain Injury Induced Bone Loss Singleton, Quante Vaibhav, Kumar Braun, Molly Patel, Chandani Khayrullin, Andrew Mendhe, Bharati Lee, Byung R. Kolhe, Ravindra Kaiser, Helen Awad, Mohamed E. Fariyike, Tunde Elsayed, Ranya Elsalanty, Mohammed Isales, Carlos M. Liu, Yutao Hamrick, Mark W. Dhandapani, Krishnan M. Fulzele, Sadanand Cells Article Traumatic brain injury (TBI) is a major source of worldwide morbidity and mortality. Patients suffering from TBI exhibit a higher susceptibility to bone loss and an increased rate of bone fractures; however, the underlying mechanisms remain poorly defined. Herein, we observed significantly lower bone quality and elevated levels of inflammation in bone and bone marrow niche after controlled cortical impact-induced TBI in in vivo CD-1 mice. Further, we identified dysregulated NF-κB signaling, an established mediator of osteoclast differentiation and bone loss, within the bone marrow niche of TBI mice. Ex vivo studies revealed increased osteoclast differentiation in bone marrow-derived cells from TBI mice, as compared to sham injured mice. We also found bone marrow derived extracellular vesicles (EVs) from TBI mice enhanced the colony forming ability and osteoclast differentiation efficacy and activated NF-κB signaling genes in bone marrow-derived cells. Additionally, we showed that miRNA-1224 up-regulated in bone marrow-derived EVs cargo of TBI. Taken together, we provide evidence that TBI-induced inflammatory stress on bone and the bone marrow niche may activate NF-κB leading to accelerated bone loss. Targeted inhibition of these signaling pathways may reverse TBI-induced bone loss and reduce fracture rates. MDPI 2019-01-17 /pmc/articles/PMC6356398/ /pubmed/30658394 http://dx.doi.org/10.3390/cells8010063 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Singleton, Quante Vaibhav, Kumar Braun, Molly Patel, Chandani Khayrullin, Andrew Mendhe, Bharati Lee, Byung R. Kolhe, Ravindra Kaiser, Helen Awad, Mohamed E. Fariyike, Tunde Elsayed, Ranya Elsalanty, Mohammed Isales, Carlos M. Liu, Yutao Hamrick, Mark W. Dhandapani, Krishnan M. Fulzele, Sadanand Bone Marrow Derived Extracellular Vesicles Activate Osteoclast Differentiation in Traumatic Brain Injury Induced Bone Loss |
title | Bone Marrow Derived Extracellular Vesicles Activate Osteoclast Differentiation in Traumatic Brain Injury Induced Bone Loss |
title_full | Bone Marrow Derived Extracellular Vesicles Activate Osteoclast Differentiation in Traumatic Brain Injury Induced Bone Loss |
title_fullStr | Bone Marrow Derived Extracellular Vesicles Activate Osteoclast Differentiation in Traumatic Brain Injury Induced Bone Loss |
title_full_unstemmed | Bone Marrow Derived Extracellular Vesicles Activate Osteoclast Differentiation in Traumatic Brain Injury Induced Bone Loss |
title_short | Bone Marrow Derived Extracellular Vesicles Activate Osteoclast Differentiation in Traumatic Brain Injury Induced Bone Loss |
title_sort | bone marrow derived extracellular vesicles activate osteoclast differentiation in traumatic brain injury induced bone loss |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356398/ https://www.ncbi.nlm.nih.gov/pubmed/30658394 http://dx.doi.org/10.3390/cells8010063 |
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