PMID- 38015348 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20231201 IS - 2662-8651 (Electronic) IS - 2662-8651 (Linking) VI - 4 IP - 1 DP - 2023 Nov 28 TI - Osteopontin enhances the effect of treadmill training and promotes functional recovery after spinal cord injury. PG - 44 LID - 10.1186/s43556-023-00154-y [doi] LID - 44 AB - 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. CI - (c) 2023. The Author(s). FAU - Wang, Yunhang AU - Wang Y AD - Department of Rehabilitation Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China. AD - Department of Rehabilitation, Zhejiang University School of Medicine Second Affiliated Hospital, 88 Jiefang Road, Hangzhou, Zhejiang, 310009, China. FAU - Su, Hong AU - Su H AD - Department of Rehabilitation Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China. FAU - Zhong, Juan AU - Zhong J AD - Department of Rehabilitation Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China. FAU - Zhan, Zuxiong AU - Zhan Z AD - Department of Rehabilitation Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China. FAU - Zhao, Qin AU - Zhao Q AD - Department of Rehabilitation Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China. FAU - Liu, Yuan AU - Liu Y AD - State Key Laboratory of Trauma, Burns and Combined Injury, Department of Special War Wound, Daping Hospital, Army Medical University, Chongqing, 400042, China. FAU - Li, Sen AU - Li S AD - State Key Laboratory of Trauma, Burns and Combined Injury, Department of Special War Wound, Daping Hospital, Army Medical University, Chongqing, 400042, China. FAU - Wang, Haiyan AU - Wang H AD - State Key Laboratory of Trauma, Burns and Combined Injury, Department of Special War Wound, Daping Hospital, Army Medical University, Chongqing, 400042, China. FAU - Yang, Ce AU - Yang C AD - State Key Laboratory of Trauma, Burns and Combined Injury, Department of Special War Wound, Daping Hospital, Army Medical University, Chongqing, 400042, China. FAU - Yu, Lehua AU - Yu L AD - Department of Rehabilitation Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China. FAU - Tan, Botao AU - Tan B AD - Department of Rehabilitation Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China. 303518@cqmu.edu.cn. FAU - Yin, Ying AU - Yin Y AD - Department of Rehabilitation Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China. 300735@cqmu.edu.cn. LA - eng GR - 81702221/National Natural Science Foundation of China/ GR - 82002377/National Natural Science Foundation of China/ GR - cstc2020jcyj-msxm0651/Natural Science Foundation of Chongqing/ GR - cstc2019jcyj-msxmX0195/Natural science Foundation of Chongqing/ GR - 2020MSXM108/Chongqing Municipal Science and Technology Bureau and Health Commission/ PT - Journal Article DEP - 20231128 PL - Singapore TA - Mol Biomed JT - Molecular biomedicine JID - 9918283581406676 PMC - PMC10684450 OTO - NOTNLM OT - Functional recovery OT - Osteopontin OT - Spinal cord injury OT - Treadmill training COIS- There are no conflicts of interest to disclose in the submission of this manuscript. On behalf of all the authors, I affirm that the research presented here is original, has not been previously published, and is not under consideration for publication elsewhere, whether in full or in part. Furthermore, all the named authors have thoroughly reviewed and provided their approval for this enclosed manuscript. EDAT- 2023/11/28 12:42 MHDA- 2023/11/28 12:43 PMCR- 2023/11/28 CRDT- 2023/11/28 11:13 PHST- 2023/07/08 00:00 [received] PHST- 2023/11/05 00:00 [accepted] PHST- 2023/11/28 12:43 [medline] PHST- 2023/11/28 12:42 [pubmed] PHST- 2023/11/28 11:13 [entrez] PHST- 2023/11/28 00:00 [pmc-release] AID - 10.1186/s43556-023-00154-y [pii] AID - 154 [pii] AID - 10.1186/s43556-023-00154-y [doi] PST - epublish SO - Mol Biomed. 2023 Nov 28;4(1):44. doi: 10.1186/s43556-023-00154-y.