Spinal cord injury (SCI) induced catastrophic neurological disability is often incurable at present. The injury triggered immediately oligodendrocytes loss and overwhelming demyelination are regarded as an insurmountable barrier to SCI recovery. To date, effective strategy to promote the endogenous oligodendrocytes replacement post SCI remains elusive. Epigenetic modifications are emerging as critical molecular switches of gene expression in CNS. However, the epigenetic mechanisms underlying oligodendrogenesis post SCI yet to be discovered. In this study, we report that H3K27me3 demethylase JMJD3 exists as a pivotal epigenetic regulator which manipulates the endogenous oligodendrogenesis post SCI. We found that JMJD3 inhibition promotes the oligodendrocyte linage commitment of neural stem/progenitor cells (NPCs) in vitro and in vivo. Moreover, we demonstrated that JMJD3 inhibition mediated SAPK/JNK signaling inactivation is functionally necessary for endogenous oligodendrocyte-lineage commitment post SCI. Our results also suggested that JMJD3 is downstream of SAPK/JNK pathway, and capable of translates SCI induced SAPK/JNK signaling into epigenetic codes readable by spinal cord endogenous NPCs. Taken together, our findings provide novel evidence of JMJD3 mediated oligodendrocyte-lineage commitment orchestration post SCI, which would be a potential epigenetic approach to induce the mature mammalian endogenous recovery.
The purpose of this study is to investigate the role of microRNA-125b (miR-125b) and its mechanism in spinal cord injury (SCI) by targeting Smurf1. After loss- and gain-function approaches were conducted in SCI rat models and neural stem cells (NSCs) isolated from foetal rats, the Basso-Beattie-Bresnahan (BBB) score was calculated, and related protein expression was determined by Western blot analysis and cell apoptosis by TUNEL staining. NSC viability was detected by CCK-8, migration abilities by Transwell assay and apoptosis by flow cytometry. The relationship between miR-125b, Smurf1 and KLF2 was evaluated by dual-luciferase reporter gene experiments, Co-IP and in vivo ubiquitin modification assays. Inhibition of miR-125b and KLF2 and the up-regulation of Smurf1 and ATF2 were observed in SCI rats. BBB scores were elevated, the expression of Nestin, NeuN, GFAP, NF-200 and Bcl-2 protein was enhanced but that of Bax protein was reduced, and cell apoptosis was inhibited in SCI rats after up-regulating miR-125b or silencing ATF2. Smurf1 was a target gene of miR-125b, which promoted KLF2 degradation through its E3 ubiquitin ligase function, and KLF2 repressed the expression of ATF2 in NSCs. The results in vivo were replicated in vitro. miR-125b overexpression promotes neurological function recovery after SCI. 相似文献
Reactive gliosis, also known as glial scar formation, is an inflammatory response characterized by the proliferation of microglia and astrocytes as well as astrocytic hypertrophy following injury in the central nervous system (CNS). The glial scar forms a physical and molecular barrier to isolate the injured area from adjacent normal nervous tissue for re-establishing the integrity of the CNS. It prevents the further spread of cellular damage but represents an obstacle to regrowing axons. In this review, we integrated the current findings to elucidate the tightly reciprocal modulation between activated microglia and astrocytes in reactive gliosis and proposed that modification of cellular response to the injury or cellular reprogramming in the glial scar could lead advances in axon regeneration and functional recovery after the CNS injury. 相似文献
Inactivation of glycogen synthase kinase 3 (GSK3) has been shown to mediate axon growth during development and regeneration. Phosphorylation of GSK3 by the kinase Akt is well known to be the major mechanism by which GSK3 is inactivated. However, whether such regulatory mechanism of GSK3 inactivation is used in neurons to control axon growth has not been directly studied. Here by using GSK3 mutant mice, in which GSK3 is insensitive to Akt-mediated inactivation, we show that sensory axons regenerate normally in vitro and in vivo after peripheral axotomy. We also find that GSK3 in sensory neurons of the mutant mice is still inactivated in response to peripheral axotomy and such inactivation is required for sensory axon regeneration. Lastly, we provide evidence that GSK3 activity is negatively regulated by PI3K signaling in the mutant mice upon peripheral axotomy, and the PI3K–GSK3 pathway is functionally required for sensory axon regeneration. Together, these results indicate that in response to peripheral nerve injury GSK3 inactivation, regulated by an alternative mechanism independent of Akt-mediated phosphorylation, controls sensory axon regeneration. 相似文献
##正## In this study a lumbar spinal fusion animal model is established to assess the effect of spinal fusion cage,and explore theminimum area ratio of titanium cage section to vertebral section that ensures bone healing and biomechanical property.Lumbarcorpectomy was conducted by posterolateral approach with titanium cage implantation combined with plate fixation.Titaniumcages with the same length but different diameters were used.After implantation of titanium cages,the progress of bone healingwas observed and the bone biomechanical properties were measured,including deformation and displacement in axial compression,flexion,extension,and lateral bending motion.The factors affecting the in vivo growth of spine supporting body wereanalyzed.The results show that the area ratio of titanium cage section to vertebral section should reach 1/2 to ensure the bonehealing,sufficient bone intensity and biomechanical properties.Some bone healing indicators,such as BMP,suggest that there isa relationship between the peak time and the peak value of bone formation and metabolism markers and the bone healing strength. 相似文献
Magnesium-based alloys are frequently reported as potential biodegradable orthopedic implant materials. Controlling the degradation rate and mechanical integrity of magnesium alloys in the physiological environment is the key to their applications. In this study, calcium phosphate (Ca-P) coating was prepared on AZ60 magnesium alloy using phosphating technology. AZ60 samples were immersed in a phosphating solution at 37 ± 2 °C for 30 min, and the solution pH was adjusted to 2.6 to 2.8 by adding NaOH solution. Then, the samples were dried in an attemperator at 60 °C. The degradation behavior was studied in vivo using Ca-P coated and uncoated magnesium alloys. Samples of these two different materials were implanted into rabbit femora, and the corrosion resistances were evaluated after 1, 2, and 3 months. The Ca-P coated samples corroded slower than the uncoated samples with prolonged time. Significant differences (p < 0.05) in mass losses and corrosion rates between uncoated samples and Ca-P coated samples were observed by micro-computed tomography. The results indicate that the Ca-P coating could slow down the degradation of magnesium alloy in vivo. 相似文献