Wang Yunhang, Su Hong, Zhong Juan, Zhan Zuxiong, Zhao Qin, Liu Yuan, Li Sen, Wang Haiyan, Yang Ce, Yu Lehua, Tan Botao, Yin Ying
Department of Rehabilitation Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
Department of Rehabilitation, Zhejiang University School of Medicine Second Affiliated Hospital, 88 Jiefang Road, Hangzhou, Zhejiang, 310009, China.
Mol Biomed. 2023 Nov 28;4(1):44. doi: 10.1186/s43556-023-00154-y.
In this study, we examined the combined impact of osteopontin (OPN) and treadmill training on mice with spinal cord injury (SCI). OPN was overexpressed by injecting AAV9-SPP1-GFP into the sensorimotor cortex, followed by a left incomplete C5 crush injury two weeks later. Mice (Ex or Ex + OPN group) were trained at 50% maximum running speed for 8 weeks. To analyze the effects, we used biotinylated dextran amine (BDA) for tracing the corticospinal tract (CST) and performed Western blotting and immunohistochemical methods to assess the activation of the mammalian target of rapamycin (mTOR). We also examined axonal regeneration and conducted behavioral tests to measure functional recovery. The results demonstrated that treadmill training promoted the expression of neurotrophic factors such as brain-derived neurotrophic factor (BNDF) and insulin-like growth factor I (IGF-1) and activated mTOR signaling. OPN amplified the effect of treadmill training on activating mTOR signaling indicated by upregulated phosphorylation of ribosomal protein S6 kinase (S6). The combination of OPN and exercise further promoted functional recovery and facilitated limited CST axonal regeneration which did not occur with treadmill training and OPN treatment alone. These findings indicate that OPN enhances the effects of treadmill training in the treatment of SCI and offer new therapeutic insights for spinal cord injury.
在本研究中，我们检测了骨桥蛋白（OPN）和跑步机训练对脊髓损伤（SCI）小鼠的联合影响。通过向感觉运动皮层注射AAV9-SPP1-GFP使OPN过表达，两周后进行左侧C5不完全挤压损伤。对小鼠（Ex组或Ex + OPN组）以最大跑步速度的50%进行8周训练。为分析其效果，我们使用生物素化葡聚糖胺（BDA）追踪皮质脊髓束（CST），并采用蛋白质免疫印迹法和免疫组化方法评估雷帕霉素哺乳动物靶点（mTOR）的激活情况。我们还检测了轴突再生，并进行行为测试以测量功能恢复情况。结果表明，跑步机训练促进了脑源性神经营养因子（BDNF）和胰岛素样生长因子I（IGF-1）等神经营养因子的表达，并激活了mTOR信号通路。OPN增强了跑步机训练对激活mTOR信号通路的作用，表现为核糖体蛋白S6激酶（S6）磷酸化上调。OPN与运动的联合进一步促进了功能恢复，并促进了有限的CST轴突再生，而单独的跑步机训练和OPN治疗均未出现这种情况。这些发现表明，OPN增强了跑步机训练在治疗SCI中的效果，并为脊髓损伤提供了新的治疗思路。
