Fei Chen, Shangze Li, Ji Wu, Qunfeng Guo, Haibin Wang, Bin Ni, Jun Yang
{"title":"源自小鼠骨髓间充质干细胞的外泌体通过 miR-155- 5p/Trim32 轴抑制核浆细胞凋亡","authors":"Fei Chen, Shangze Li, Ji Wu, Qunfeng Guo, Haibin Wang, Bin Ni, Jun Yang","doi":"10.2174/1566524023666230816090843","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Lower back pain, shown to be strongly associated with IVDD, affects approximately 60%-80% of adults and has a considerable societal and economic impact. Evidence suggests that IVDD, caused by abnormal apoptosis of nucleus pulposus cells (NPCs), can be treated using MSC-derived exosomes.</p><p><strong>Objective: </strong>This study aimed to evaluate the role of miR155-5p/Trim32 in intervertebral disc disease (IVDD) and elucidate the underlying molecular mechanisms. Deregulating miR-155 has been shown to promote Fas-mediated apoptosis in human IVDD. Evidence also suggests that tripartite motif (TRIM)-containing protein 32 (Trim32) is regulated by miR-155. However, the role of miR155-5p/Trim32 in IVDD remains unclear.</p><p><strong>Methods: </strong>Cell viability was checked using CCK-8 kits, and flow cytometry was used to analyze cell cycle and apoptosis. Cell migration was measured with a Transwell assay, while a luciferase assay was adopted to study how miR-155-5p interacts with Trim32. The roles of Trim32 and miR-155-5p were studied by silencing or up-regulating them in NPCs, while qPCR and immunoblots were used to evaluate mRNA and protein changes, respectively.</p><p><strong>Results: </strong>TNF-α treatment significantly inhibited cell viability but promoted Trim32 expression in primary mouse NPCs. Administration of bone marrow mesenchymal stem cells (BMSCs) attenuated primary NPC cell cycle arrest and apoptosis induced by TNF- α. BMSCs-derived exosomes could be taken up by NPCs to inhibit TNF-α-induced cell cycle arrest and apoptosis through miR-155-5p. Examination of the underlying mechanism showed that miR-155-5p targeted Trim32. Moreover, Trim32 overexpression inhibited the effect of BMSCs-derived exosomes on primary mouse NPC cell apoptosis induced by TNF-α.</p><p><strong>Conclusion: </strong>Overall, these findings suggest that exosomes from BMSCs can suppress TNF-α-induced cell cycle arrest and apoptosis in primary mouse NPCs through the delivery of miR-155-5p by targeting Trim32. This study provides a promising therapeutic strategy for IVDD.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":null,"pages":null},"PeriodicalIF":2.2000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Exosomes derived from Mouse Bone Marrow Mesenchymal Stem Cells Attenuate Nucleus Pulposus Cell Apoptosis via the miR-155- 5p/Trim32 Axis.\",\"authors\":\"Fei Chen, Shangze Li, Ji Wu, Qunfeng Guo, Haibin Wang, Bin Ni, Jun Yang\",\"doi\":\"10.2174/1566524023666230816090843\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Lower back pain, shown to be strongly associated with IVDD, affects approximately 60%-80% of adults and has a considerable societal and economic impact. Evidence suggests that IVDD, caused by abnormal apoptosis of nucleus pulposus cells (NPCs), can be treated using MSC-derived exosomes.</p><p><strong>Objective: </strong>This study aimed to evaluate the role of miR155-5p/Trim32 in intervertebral disc disease (IVDD) and elucidate the underlying molecular mechanisms. Deregulating miR-155 has been shown to promote Fas-mediated apoptosis in human IVDD. Evidence also suggests that tripartite motif (TRIM)-containing protein 32 (Trim32) is regulated by miR-155. However, the role of miR155-5p/Trim32 in IVDD remains unclear.</p><p><strong>Methods: </strong>Cell viability was checked using CCK-8 kits, and flow cytometry was used to analyze cell cycle and apoptosis. Cell migration was measured with a Transwell assay, while a luciferase assay was adopted to study how miR-155-5p interacts with Trim32. The roles of Trim32 and miR-155-5p were studied by silencing or up-regulating them in NPCs, while qPCR and immunoblots were used to evaluate mRNA and protein changes, respectively.</p><p><strong>Results: </strong>TNF-α treatment significantly inhibited cell viability but promoted Trim32 expression in primary mouse NPCs. Administration of bone marrow mesenchymal stem cells (BMSCs) attenuated primary NPC cell cycle arrest and apoptosis induced by TNF- α. BMSCs-derived exosomes could be taken up by NPCs to inhibit TNF-α-induced cell cycle arrest and apoptosis through miR-155-5p. Examination of the underlying mechanism showed that miR-155-5p targeted Trim32. Moreover, Trim32 overexpression inhibited the effect of BMSCs-derived exosomes on primary mouse NPC cell apoptosis induced by TNF-α.</p><p><strong>Conclusion: </strong>Overall, these findings suggest that exosomes from BMSCs can suppress TNF-α-induced cell cycle arrest and apoptosis in primary mouse NPCs through the delivery of miR-155-5p by targeting Trim32. This study provides a promising therapeutic strategy for IVDD.</p>\",\"PeriodicalId\":10873,\"journal\":{\"name\":\"Current molecular medicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2024-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current molecular medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2174/1566524023666230816090843\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current molecular medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/1566524023666230816090843","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Exosomes derived from Mouse Bone Marrow Mesenchymal Stem Cells Attenuate Nucleus Pulposus Cell Apoptosis via the miR-155- 5p/Trim32 Axis.
Background: Lower back pain, shown to be strongly associated with IVDD, affects approximately 60%-80% of adults and has a considerable societal and economic impact. Evidence suggests that IVDD, caused by abnormal apoptosis of nucleus pulposus cells (NPCs), can be treated using MSC-derived exosomes.
Objective: This study aimed to evaluate the role of miR155-5p/Trim32 in intervertebral disc disease (IVDD) and elucidate the underlying molecular mechanisms. Deregulating miR-155 has been shown to promote Fas-mediated apoptosis in human IVDD. Evidence also suggests that tripartite motif (TRIM)-containing protein 32 (Trim32) is regulated by miR-155. However, the role of miR155-5p/Trim32 in IVDD remains unclear.
Methods: Cell viability was checked using CCK-8 kits, and flow cytometry was used to analyze cell cycle and apoptosis. Cell migration was measured with a Transwell assay, while a luciferase assay was adopted to study how miR-155-5p interacts with Trim32. The roles of Trim32 and miR-155-5p were studied by silencing or up-regulating them in NPCs, while qPCR and immunoblots were used to evaluate mRNA and protein changes, respectively.
Results: TNF-α treatment significantly inhibited cell viability but promoted Trim32 expression in primary mouse NPCs. Administration of bone marrow mesenchymal stem cells (BMSCs) attenuated primary NPC cell cycle arrest and apoptosis induced by TNF- α. BMSCs-derived exosomes could be taken up by NPCs to inhibit TNF-α-induced cell cycle arrest and apoptosis through miR-155-5p. Examination of the underlying mechanism showed that miR-155-5p targeted Trim32. Moreover, Trim32 overexpression inhibited the effect of BMSCs-derived exosomes on primary mouse NPC cell apoptosis induced by TNF-α.
Conclusion: Overall, these findings suggest that exosomes from BMSCs can suppress TNF-α-induced cell cycle arrest and apoptosis in primary mouse NPCs through the delivery of miR-155-5p by targeting Trim32. This study provides a promising therapeutic strategy for IVDD.
期刊介绍:
Current Molecular Medicine is an interdisciplinary journal focused on providing the readership with current and comprehensive reviews/ mini-reviews, original research articles, short communications/letters and drug clinical trial studies on fundamental molecular mechanisms of disease pathogenesis, the development of molecular-diagnosis and/or novel approaches to rational treatment. The reviews should be of significant interest to basic researchers and clinical investigators in molecular medicine. Periodically the journal invites guest editors to devote an issue on a basic research area that shows promise to advance our understanding of the molecular mechanism(s) of a disease or has potential for clinical applications.