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

Quante Singleton, Kumar Vaibhav, Molly Braun, Chandani Patel, Andrew Khayrullin, Bharati Mendhe, Byung R Lee, Ravindra Kolhe, Helen Kaiser, Mohamed E Awad, Tunde Fariyike, Ranya Elsayed, Mohammed Elsalanty, Carlos M Isales, Yutao Liu, Mark W Hamrick, Krishnan M Dhandapani, Sadanand Fulzele

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalFuel Cells
Volume8
Issue number1
DOIs
StatePublished - Jan 17 2019

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Keywords

  • Animals
  • Biomarkers/metabolism
  • Bone Marrow/metabolism
  • Bone Resorption/etiology
  • Brain Injuries, Traumatic/complications
  • Cell Differentiation
  • Cytokines/metabolism
  • Extracellular Vesicles/metabolism
  • Femur/diagnostic imaging
  • Gene Expression Regulation
  • Inflammation/genetics
  • Male
  • Mice
  • MicroRNAs/genetics
  • NF-kappa B/metabolism
  • Osteoclasts/cytology
  • Osteogenesis
  • Signal Transduction
  • X-Ray Microtomography

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