Li Wang1,2, Zhiwen Song1, Hongjun Zou1, Haining Chen1, Yong Hu1, Xiangnan Li3, Jinbo Liu4. 1. Department of Orthopedics, The Third Affiliated Hospital, Soochow University, No.185 Juqian Street, Changzhou, 213003, Jiangsu, China. 2. Department of Orthopedics, The Third People's Hospital of Yancheng City, Yancheng, 224001, Jiangsu, China. 3. Department of Anesthesia, The Third People's Hospital of Yancheng City, Yancheng, 224001, Jiangsu, China. 4. Department of Spine, The Third Affiliated Hospital, Soochow University, Changzhou, 213003, Jiangsu, China. czljbljb@126.com.
Abstract
PURPOSE: The present work focused on exploring the role of circRNA3616 in neuronal inflammation and apoptosis in spinal cord injury (SCI). METHODS: The SCI mouse model and circRNA3616 knockdown SCI mouse model were established. This work focused on assessing the mouse locomotor function using Basso Mouse Scale (BMS) and BMS subscore. Hematoxylin-eosin (HE) staining and Tunel staining were conducted, while myeloperoxidase (MPO) activity was also detected on spinal cord tissues. We also knocked down circRNA3616 expression in NSC-34 cells. Meanwhile, the SCI cell model was established by oxygen glucose deprivation (OGD) in NSC-34 cells. Moreover, we conducted dual-luciferase reporter gene assay. Flow cytometry (FCM) was conducted to detect SCI cell apoptosis, whereas cell counting kit-8 (CCK-8) assay was performed to analyze cell viability. This study also implemented enzyme-linked immunosorbent assay to detect inflammatory factors in spinal cord tissues, serum, and cells. RESULTS: CircRNA3616 knockdown reduced the damage, inflammatory response, apoptosis, and MPO activity in SCI mouse serum and spinal cord tissues. CircRNA3616 knockdown increased BMS and BMS subscore of SCI mice. CircRNA3616 up-regulated TLR4 expression by sponging miR-137. CircRNA3616 knockdown inhibited the TLR4, p-IkBα, p-p65/p65 protein expression, while promoting IkBα protein expression within SCI mouse spinal cord. TLR4 reversed circRNA3616 knockdown-induced inhibition on NF-κB pathway activity in SCI cells. CircRNA3616 knockdown attenuated neuronal cell inflammation and apoptosis via TLR4/NF-κB pathway after SCI. CONCLUSION: CircRNA3616 silencing attenuates inflammation and apoptosis in SCI by inhibiting TLR4/NF-κB activity via sponging miR-137. CircRNA3616 is the possible anti-SCI therapeutic target.
PURPOSE: The present work focused on exploring the role of circRNA3616 in neuronal inflammation and apoptosis in spinal cord injury (SCI). METHODS: The SCI mouse model and circRNA3616 knockdown SCI mouse model were established. This work focused on assessing the mouse locomotor function using Basso Mouse Scale (BMS) and BMS subscore. Hematoxylin-eosin (HE) staining and Tunel staining were conducted, while myeloperoxidase (MPO) activity was also detected on spinal cord tissues. We also knocked down circRNA3616 expression in NSC-34 cells. Meanwhile, the SCI cell model was established by oxygen glucose deprivation (OGD) in NSC-34 cells. Moreover, we conducted dual-luciferase reporter gene assay. Flow cytometry (FCM) was conducted to detect SCI cell apoptosis, whereas cell counting kit-8 (CCK-8) assay was performed to analyze cell viability. This study also implemented enzyme-linked immunosorbent assay to detect inflammatory factors in spinal cord tissues, serum, and cells. RESULTS: CircRNA3616 knockdown reduced the damage, inflammatory response, apoptosis, and MPO activity in SCI mouse serum and spinal cord tissues. CircRNA3616 knockdown increased BMS and BMS subscore of SCI mice. CircRNA3616 up-regulated TLR4 expression by sponging miR-137. CircRNA3616 knockdown inhibited the TLR4, p-IkBα, p-p65/p65 protein expression, while promoting IkBα protein expression within SCI mouse spinal cord. TLR4 reversed circRNA3616 knockdown-induced inhibition on NF-κB pathway activity in SCI cells. CircRNA3616 knockdown attenuated neuronal cell inflammation and apoptosis via TLR4/NF-κB pathway after SCI. CONCLUSION: CircRNA3616 silencing attenuates inflammation and apoptosis in SCI by inhibiting TLR4/NF-κB activity via sponging miR-137. CircRNA3616 is the possible anti-SCI therapeutic target.
Authors: Yu Yao; Xin Zhang; Jun Xu; Feng Gao; Yanni Wu; Xintao Cui; Li Wei; Jie Jiang; Xintao Wang Journal: Am J Transl Res Date: 2022-01-15 Impact factor: 4.060
Authors: Brian A Karamian; Nicholas Siegel; Blake Nourie; Mijail D Serruya; Robert F Heary; James S Harrop; Alexander R Vaccaro Journal: J Orthop Traumatol Date: 2022-01-06