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Cells. 2019 Jan 17;8(1). pii: E63. doi: 10.3390/cells8010063.

Bone Marrow Derived Extracellular Vesicles Activate Osteoclast Differentiation in Traumatic Brain Injury Induced Bone Loss.

Author information

1
Departments of Orthopedic Surgery, Augusta University, Augusta, GA 30912, USA. qsingleton@augusta.edu.
2
Department of Neurosurgery, Augusta University, Augusta, GA 30912, USA. kvaibhav@augusta.edu.
3
Department of Neurosurgery, Augusta University, Augusta, GA 30912, USA. mobraun@augusta.edu.
4
Departments of Orthopedic Surgery, Augusta University, Augusta, GA 30912, USA. chapatel@augusta.edu.
5
Cell Biology and Anatomy, Augusta University, Augusta, GA 30912, USA. akhayrullin@augusta.edu.
6
Cell Biology and Anatomy, Augusta University, Augusta, GA 30912, USA. bmendhe@augusta.edu.
7
Departments of Orthopedic Surgery, Augusta University, Augusta, GA 30912, USA. blee@augusta.edu.
8
Departments of Pathology, Augusta University, Augusta, GA 30912, USA. rkolhe@augusta.edu.
9
Cell Biology and Anatomy, Augusta University, Augusta, GA 30912, USA. hkaiser@augusta.edu.
10
Department of Oral biology, Augusta University, Augusta, GA 30912, USA. moawad@augusta.edu.
11
Department of Neurosurgery, Augusta University, Augusta, GA 30912, USA. bfariyike@augusta.edu.
12
Departments of Pathology, Augusta University, Augusta, GA 30912, USA. relsayed@augusta.edu.
13
Departments of Pathology, Augusta University, Augusta, GA 30912, USA. melsalanty@augusta.edu.
14
Departments of Orthopedic Surgery, Augusta University, Augusta, GA 30912, USA. cisales@augusta.edu.
15
Institute of Regenerative and Reparative Medicine, Georgia Regents University, Augusta, GA 30912, USA. cisales@augusta.edu.
16
Cell Biology and Anatomy, Augusta University, Augusta, GA 30912, USA. yutliu@augusta.edu.
17
Cell Biology and Anatomy, Augusta University, Augusta, GA 30912, USA. mhamrick@augusta.edu.
18
Institute of Regenerative and Reparative Medicine, Georgia Regents University, Augusta, GA 30912, USA. mhamrick@augusta.edu.
19
Department of Neurosurgery, Augusta University, Augusta, GA 30912, USA. kdhandapani@augusta.edu.
20
Departments of Orthopedic Surgery, Augusta University, Augusta, GA 30912, USA. sfulzele@augusta.edu.
21
Institute of Regenerative and Reparative Medicine, Georgia Regents University, Augusta, GA 30912, USA. sfulzele@augusta.edu.

Abstract

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.

KEYWORDS:

bone loss; extracellular vesicles; traumatic brain injury

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