Long Non-coding RNAs in Traumatic Brain Injury Accelerated Fracture Healing

Abstract

It is commonly observed that patients with bone fracture concomitant with traumatic brain injury (TBI) had significantly increased fracture healing, but the underlying mechanisms were not fully revealed. Long non-coding RNAs (lncRNAs) are known to play complicated roles in bone homeostasis, but their role in TBI accelerated fracture was rarely reported. The present study was designed to determine the role of lncRNAs in TBI accelerated fracture via transcriptome sequencing and further bioinformatics analyses. Blood samples from three fracture-only patients, three fracture concomitant with TBI patients, and three healthy controls were harvested and were subsequently subjected to transcriptome lncRNA sequencing. Differentially expressed genes were identified, and pathway enrichment was performed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. High-dimensional data visualization by self-organizing map (SOM) machine learning was applied to further interpret the data. An xCell method was then used to predict cellular behavior in all samples based on gene expression profiles, and an lncRNA–cell interaction network was generated. A total of 874 differentially expressed genes were identified, of which about 26% were lncRNAs. Those identified lncRNAs were mainly enriched on TBI-related and damage repair-related pathways. SOM analyses revealed that those differentially expressed lncRNAs could be divided into three major module implications and were mainly enriched on transcriptional regulation and immune-related signal pathways, which promote us to further explore cellular behaviors based on differentially expressed lncRNAs. We have predicted that basophils, CD8+ T effector memory cells, B cells, and naïve B cells were significantly downregulated, while microvascular endothelial cells were predicted to be significantly upregulated in the Fr/TBI group, was the lowest and highest, respectively. ENSG00000278905, ENSG00000240980, ENSG00000255670, and ENSG00000196634 were the most differentially expressed lncRNAs related to all changes of cellular behavior. The present study has revealed for the first time that several critical lncRNAs may participate in TBI accelerated fracture potentially via regulating cellular behaviors of basophils, cytotoxic T cells, B cells, and endothelial cells.

Long Noncoding RNA VLDLR-AS1 Levels in Serum Correlate with Combat-Related Chronic Mild Traumatic Brain Injury and Depression Symptoms in US Veterans

“…While serum lncRNA biomarkers for rmTBI have not been described previously, the role of lncRNAs in brain injury has been demonstrated. MALAT1, NEAT1, SNHG1, MEG3, HOTAIR were shown to be involved in inflammation angiogenesis, apoptosis and cell proliferation pathways in the brain, and their levels changed in the brain tissue in mouse models of TBI [73][74][75][76][77][78]. These studies did not measure circulating blood levels of lncRNA in mouse models of TBI.…”

Interoceptive regulation of skeletal tissue homeostasis and repair

“… Fracture-only: 3 Fracture with TBI: 3 Healthy controls: 3 In the fracture with TBI group, several critical lncRNAs (including ENSG00000278905, ENSG00000240980, ENSG00000255670, and ENSG00000196634) were involved in regulating the cellular activity of basophils, cytotoxic T cells, B cells, and endothelial cells. 2021 216 TBI: 30 Femoral fracture: 30 Femoral fracture with TBI: 30 Healthy subjects: 30 Faster femoral fracture healing occurred in the femoral fracture with TBI group than in the femoral fracture-only group. BMP-2, FGF-2, IL-1β, and PDGF levels in the femoral fracture with TBI group were significantly elevated over 12 h and after 4 weeks (indicating their potential involvement in accelerated fracture healing among patients with TBI).…”