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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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.
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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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