The regeneration of the blood vessel system post spinal cord injury (SCI) is essential for the repair of neurological function. As a significant means to regulate gene expression, epigenetic regulation of angiogenesis in SCI is still largely unknown. Here, we found that Ubiquitously Transcribed tetratricopeptide repeat on chromosome X (UTX), the histone H3K27 demethylase, increased significantly in endothelial cells post SCI. Knockdown of UTX can promote the migration and tube formation of endothelial cells. The specific knockout of UTX in endothelial cells enhanced angiogenesis post SCI accompanied with improved neurological function. In addition, we found regulation of UTX expression can change the level of microRNA 24 (miR-24) in vitro . The physical binding of UTX to the promotor of miR-24 was indicated by chromatin immunoprecipitation (ChIP) assay. Meanwhile, methylation sequencing of endothelial cells demonstrated that UTX could significantly decrease the level of methylation in the miR-24 promotor. Furthermore, miR-24 significantly abolished the promoting effect of UTX deletion on angiogenesis in vitro and in vivo . Finally, we predicted the potential target mRNAs of miR-24 related to angiogenesis. We indicate that UTX deletion can epigenetically promote the vascular regeneration and functional recovery post SCI by forming a regulatory network with miR-24.

Summary Objective To measure in vivo thicknesses of the facet joint subchondral bone across genders, age groups, with or without low back pain symptom groups and spinal levels. Methods Lumbar (L1–L2 to L5-S1) magnetic resonance (MR) imaging was performed in 81 subjects (41 males and 40 females, mean age 37.6 years). Thicknesses of the subchondral bone were measured in 1,620 facet joints using the MR images with custom-written image processing algorithms together with a multi-threshold segmentation technique using each facet joint’s middle axial-slice. This method was validated with 12 cadaver facet joints, scanned with both MR and micro-computed tomography images. Results An overall average thickness value for the 1,620 analyzed joints was measured as 1.56 ± 0.01 mm. The subchondral bone thickness values showed significant increases with successive lower spinal levels in the subjects without low back pain. The facet joint subchondral bone thickness in asymptomatic females was much smaller than in asymptomatic males. Mean subchondral bone thickness in the superior facet was greater than that in the inferior facet in both female and male asymptomatic subjects. Conclusions This study is the first to quantitatively show subchondral bone thickness using a validated MR-based technique. The subchondral bone thickness was greater in asymptomatic males and increased with each successive lower spinal level. These findings may suggest that the subchondral bone thickness increases with loading. Furthermore, the superior facet subchondral bone was thicker than the inferior facet in all cases regardless of gender, age or spinal level in the subjects without low back pain. More research is needed to link subchondral bone microstructure to facet joint kinematics and spinal loads.

Spinal cord injury (SCI) is a catastrophic event mainly involving neuronal apoptosis and axonal disruption, and it causes severe motor and sensory deficits. Due to the complicated pathological process of SCI, there is currently still a lack of effective treatment for SCI. Microglia, a type of immune cell residing in the central nervous system (CNS), need to respond to various stimuli to protect neuronal cells from death. It was also reported that microRNAs (miRNAs) had been identified in microglia-derived exosomes that can be taken up by neurons. However, the kinds of miRNAs in exosome cargo derived from microglia and the underlying mechanisms by which they contribute to neuroprotection after SCI remain unknown. In the present study, a contusive SCI mouse model and in vitro experiments were applied to explore the therapeutic effects of microglia-derived exosomes on neuronal apoptosis, axonal regrowth, and functional recovery after SCI. Then, miRNA analysis, rescue experiments, and luciferase activity assays for target genes were performed to confirm the role and underlying mechanism of microglia-derived exosomal miRNAs in SCI. We revealed that microglia-derived exosomes could promote neurological functional recovery by suppressing neuronal apoptosis and promoting axonal regrowth both in vivo and in vitro. MicroRNA-151-3p is abundant in microglia-derived exosomes and is necessary for mediating the neuroprotective effect of microglia-derived exosomes for SCI repair. Luciferase activity assays reported that P53 was the target gene for miR-151-3p and that p53/p21/CDK1 signaling cascades may be involved in the modulation of neuronal apoptosis and axonal regrowth by microglia-derived exosomal microRNA-151-3p. In conclusion, our data demonstrated that microglia-derived exosomes (microglia-Exos) might be a promising, cell-free approach for the treatment of SCI. MicroRNA-151-3p is the key molecule in microglia-derived exosomes that mediates the neuroprotective effects of SCI treatments.