Preprint Article Version 1 This version is not peer-reviewed

Bone marrow derived extracellular vesicles activate osteoclast differentiation in traumatic brain injury induced bone loss

Version 1 : Received: 22 October 2018 / Approved: 23 October 2018 / Online: 23 October 2018 (08:56:08 CEST)

A peer-reviewed article of this Preprint also exists.

Singleton, Q.; Vaibhav, K.; Braun, M.; Patel, C.; Khayrullin, A.; Mendhe, B.; Lee, B.R.; Kolhe, R.; Kaiser, H.; Awad, M.E.; Fariyike, T.; Elsayed, R.; Elsalanty, M.; Isales, C.M.; Liu, Y.; Hamrick, M.W.; Dhandapani, K.M.; Fulzele, S. Bone Marrow Derived Extracellular Vesicles Activate Osteoclast Differentiation in Traumatic Brain Injury Induced Bone Loss. Cells 2019, 8, 63. Singleton, Q.; Vaibhav, K.; Braun, M.; Patel, C.; Khayrullin, A.; Mendhe, B.; Lee, B.R.; Kolhe, R.; Kaiser, H.; Awad, M.E.; Fariyike, T.; Elsayed, R.; Elsalanty, M.; Isales, C.M.; Liu, Y.; Hamrick, M.W.; Dhandapani, K.M.; Fulzele, S. Bone Marrow Derived Extracellular Vesicles Activate Osteoclast Differentiation in Traumatic Brain Injury Induced Bone Loss. Cells 2019, 8, 63.

Journal reference: Cells 2019, 8, 63
DOI: 10.3390/cells8010063

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B 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. Finally, we found bone marrow derived extracellular vesicles (EVs) from TBI mice enhanced the colony forming ability and osteoclast differentiation efficacy of bone marrow cells and activated NFB signaling genes in bone marrow-derived cells. Taken together, we provide evidence that TBI-induced inflammatory stress on bone and the bone marrow niche may activate NFB leading to accelerated bone loss. Targeted inhibition of these signaling pathways may reverse TBI-induced bone loss and reduce fracture rates.

Subject Areas

extracellular vesicles, EVs , traumatic brain injury, bone loss, TBI

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