Exosome miR-23a-3p From Osteoblast Alleviates Spinal Cord Ischemia/Reperfusion Injury by Down-regulating KLF3-activated CCNL2 Transcription

Background: Spinal cord ischemia/reperfusion injury (SCIRI) is usually caused by spinal surgery or aortic aneurysm surgery and can eventually lead to paralysis or paraplegia and neurological dysfunction. Exosomes are considered as one of the most promising therapeutic strategies for SCIRI as they can pass the blood-spinal barrier. Previous studies have proved that exosomes secreted by osteocytes have a certain slowing effect on SCIRI. Aim: We aimed to explore the effect of osteoblast secreted exosomes on SCIRI. Methods: Firstly, neurons and osteoblasts were co-cultured under different conditions. GEO database was utilized to detect the expression of miR-23a-3p in osteoblast exosomes. SCIRI cells were treated with exosomes, and the detection was taken to prove whether miR-23a-3p could slow the progression of SCIRI. Downstream gene and the potential regulatory mechanism were explored through database and functional experiments. Results: MiR-23a-3p was highly expressed in exosomes and it slowed down the process of SCIRI. Downstream mRNA KLF3 could bind to miR-23a-3p and was highly expressed in IRI. Moreover, CCNL2 was regulated by KLF3 and was highly expressed in IRI. Rescue experiments verified that miR-23a-3p suppressed the transcription of CCNL2 by targeting KLF3. Conclusion: Exosome miR-23a-3p from osteoblast alleviates SCIRI by down-regulating KLF3-activated CCNL2 transcription.

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Salidroside Ameliorates Mitochondria-Dependent Neuronal Apoptosis after Spinal Cord Ischemia-Reperfusion Injury Partially through Inhibiting Oxidative Stress and Promoting Mitophagy

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/3549704 ◽

2020 ◽

Vol 2020 ◽

pp. 1-22

Author(s):

Changjiang Gu ◽

Linwei Li ◽

Yifan Huang ◽

Dingfei Qian ◽

Wei Liu ◽

...

Keyword(s):

Spinal Cord ◽

Reperfusion Injury ◽

Neuronal Apoptosis ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Spinal Cord Ischemia ◽

Neurological Dysfunction ◽

Spinal Cord Neurons

Ischemia-reperfusion injury is the second most common injury of the spinal cord and has the risk of neurological dysfunction and paralysis, which can seriously affect patient quality of life. Salidroside (Sal) is an active ingredient extracted from Herba Cistanche with a variety of biological attributes such as antioxidant, antiapoptotic, and neuroprotective activities. Moreover, Sal has shown a protective effect in ischemia-reperfusion injury of the liver, heart, and brain, but its effect in ischemia-reperfusion injury of the spinal cord has not been elucidated. Here, we demonstrated for the first time that Sal pretreatment can significantly improve functional recovery in mice after spinal cord ischemia-reperfusion injury and significantly inhibit the apoptosis of neurons both in vivo and in vitro. Neurons have a high metabolic rate, and consequently, mitochondria, as the main energy-supplying suborganelles, become the main injury site of spinal cord ischemia-reperfusion injury. Mitochondrial pathway-dependent neuronal apoptosis is increasingly confirmed by researchers; therefore, Sal’s effect on mitochondria naturally attracted our attention. By means of a range of experiments both in vivo and in vitro, we found that Sal can reduce reactive oxygen species production through antioxidant stress to reduce mitochondrial permeability and mitochondrial damage, and it can also enhance the PINK1-Parkin signaling pathway and promote mitophagy to eliminate damaged mitochondria. In conclusion, our results show that Sal is beneficial to the protection of spinal cord neurons after ischemia-reperfusion injury, mainly by reducing apoptosis associated with the mitochondrial-dependent pathway, among which Sal’s antioxidant and autophagy-promoting properties play an important role.

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