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Current Molecular Medicine

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ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

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Research Article

Exosomes derived from Mouse Bone Marrow Mesenchymal Stem Cells Attenuate Nucleus Pulposus Cell Apoptosis via the miR-155- 5p/Trim32 Axis

Author(s): Fei Chen, Shangze Li, Ji Wu, Qunfeng Guo, Haibin Wang, Bin Ni* and Jun Yang*

Volume 24, Issue 8, 2024

Published on: 12 September, 2023

Page: [1045 - 1055] Pages: 11

DOI: 10.2174/1566524023666230816090843

Price: $65

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Abstract

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.

Keywords: Intervertebral disc degeneration, miRNA, cell death, exosomes, mesenchymal stem cells, Trim32.

« Previous Next »
[1]
Murray CJL, Vos T, Lozano R, et al. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: A systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012; 380(9859): 2197-223.
[http://dx.doi.org/10.1016/S0140-6736(12)61689-4] [PMID: 23245608]
[2]
Hartvigsen J, Hancock MJ, Kongsted A, et al. What low back pain is and why we need to pay attention. Lancet 2018; 391(10137): 2356-67.
[http://dx.doi.org/10.1016/S0140-6736(18)30480-X] [PMID: 29573870]
[3]
Kos N, Gradisnik L, Velnar T. A brief review of the degenerative intervertebral disc disease. Med Arh 2019; 73(6): 421-4.
[http://dx.doi.org/10.5455/medarh.2019.73.421-424] [PMID: 32082013]
[4]
Virtanen IM, Karppinen J, Taimela S, et al. Occupational and genetic risk factors associated with intervertebral disc disease. Spine 2007; 32(10): 1129-34.
[http://dx.doi.org/10.1097/01.brs.0000261473.03274.5c] [PMID: 17471097]
[5]
Molinos M, Almeida CR, Caldeira J, Cunha C, Gonçalves RM, Barbosa MA. Inflammation in intervertebral disc degeneration and regeneration. J R Soc Interface 2015; 12(108): 20150429.
[http://dx.doi.org/10.1098/rsif.2015.0429] [PMID: 26040602]
[6]
Xie L, Huang W, Fang Z, et al. CircERCC2 ameliorated intervertebral disc degeneration by regulating mitophagy and apoptosis through miR-182-5p/SIRT1 axis. Cell Death Dis 2019; 10(10): 751.
[http://dx.doi.org/10.1038/s41419-019-1978-2] [PMID: 31582722]
[7]
Chen PB, Shi GX, Liu T, et al. Oxidative stress aggravates apoptosis of nucleus pulposus cells through m6a modification of MAT2A Pre-mRNA by METTL16. Oxid Med Cell Longev 2022; 2022: 1-15.
[http://dx.doi.org/10.1155/2022/4036274] [PMID: 35069973]
[8]
Saeedi P, Halabian R, Imani Fooladi AA. A revealing review of mesenchymal stem cells therapy, clinical perspectives and Modification strategies. Stem Cell Investig 2019; 6: 34.
[http://dx.doi.org/10.21037/sci.2019.08.11] [PMID: 31620481]
[9]
Pittenger MF, Discher DE, Péault BM, Phinney DG, Hare JM, Caplan AI. Mesenchymal stem cell perspective: Cell biology to clinical progress. NPJ Regen Med 2019; 4(1): 22.
[http://dx.doi.org/10.1038/s41536-019-0083-6] [PMID: 31815001]
[10]
Relation T, Yi T, Guess AJ, et al. Intratumoral delivery of interferonγ-secreting mesenchymal stromal cells repolarizes tumor-associated macrophages and suppresses neuroblastoma proliferation in vivo. Stem Cells 2018; 36(6): 915-24.
[http://dx.doi.org/10.1002/stem.2801] [PMID: 29430789]
[11]
Boháčová P, Holáň V. Mesenchymal stem cells and type 1 diabetes treatment. Vnitr Lek 2018; 64(7-8): 725-8.
[http://dx.doi.org/10.36290/vnl.2018.099] [PMID: 30441979]
[12]
Chun HJ, Kim YS, Kim BK, et al. Transplantation of human adipose-derived stem cells in a rabbit model of traumatic degeneration of lumbar discs. World Neurosurg 2012; 78(3-4): 364-71.
[http://dx.doi.org/10.1016/j.wneu.2011.12.084] [PMID: 22381275]
[13]
Stoyanov JV, Gantenbein-Ritter B, Bertolo A, et al. Role of hypoxia and growth and differentiation factor-5 on differentiation of human mesenchymal stem cells towards intervertebral nucleus pulposus-like cells. Eur Cell Mater 2011; 21: 533-47.
[http://dx.doi.org/10.22203/eCM.v021a40] [PMID: 21710444]
[14]
Zhang Y, Liu Y, Liu H, Tang WH. Exosomes: Biogenesis, biologic function and clinical potential. Cell Biosci 2019; 9(1): 19.
[http://dx.doi.org/10.1186/s13578-019-0282-2] [PMID: 30815248]
[15]
Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science 2020; 367(6478): eaau6977.
[http://dx.doi.org/10.1126/science.aau6977] [PMID: 32029601]
[16]
Zhao H, Yang L, Baddour J, et al. Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism. eLife 2016; 5: e10250.
[http://dx.doi.org/10.7554/eLife.10250] [PMID: 26920219]
[17]
O’Brien KP, Khan S, Gilligan KE, et al. Employing mesenchymal stem cells to support tumor-targeted delivery of extracellular vesicle (EV)-encapsulated microRNA-379. Oncogene 2018; 37(16): 2137-49.
[http://dx.doi.org/10.1038/s41388-017-0116-9] [PMID: 29367765]
[18]
Lu K, Li H, Yang K, et al. Exosomes as potential alternatives to stem cell therapy for intervertebral disc degeneration: In-vitro study on exosomes in interaction of nucleus pulposus cells and bone marrow mesenchymal stem cells. Stem Cell Res Ther 2017; 8(1): 108.
[http://dx.doi.org/10.1186/s13287-017-0563-9] [PMID: 28486958]
[19]
Zhu G, Yang X, Peng C, Yu L, Hao Y. Exosomal miR-532–5p from bone marrow mesenchymal stem cells reduce intervertebral disc degeneration by targeting RASSF5. Exp Cell Res 2020; 393(2): 112109.
[http://dx.doi.org/10.1016/j.yexcr.2020.112109] [PMID: 32464126]
[20]
O’Brien J, Hayder H, Zayed Y, Peng C. Overview of MicroRNA biogenesis, mechanisms of actions, and circulation. Front Endocrinol 2018; 9: 402.
[http://dx.doi.org/10.3389/fendo.2018.00402] [PMID: 30123182]
[21]
Huang W. MicroRNAs: Biomarkers, diagnostics, and therapeutics. Methods Mol Biol 2017; 1617: 57-67.
[http://dx.doi.org/10.1007/978-1-4939-7046-9_4] [PMID: 28540676]
[22]
Zech A, Ayata CK, Pankratz F, et al. MicroRNA-155 modulates P2R signaling and Th2 priming of dendritic cells during allergic airway inflammation in mice. Allergy 2015; 70(9): 1121-9.
[http://dx.doi.org/10.1111/all.12643] [PMID: 25944053]
[23]
Li X, Wang S, Mu W, et al. Reactive oxygen species reprogram macrophages to suppress antitumor immune response through the exosomal miR-155-5p/PD-L1 pathway. J Exp Clin Cancer Res 2022; 41(1): 41.
[http://dx.doi.org/10.1186/s13046-022-02244-1] [PMID: 35086548]
[24]
Zhang W, Li X, Tang Y, Chen C, Jing R, Liu T. miR-155-5p implicates in the pathogenesis of renal fibrosis via targeting SOCS1 and SOCS6. Oxid Med Cell Longev 2020; 2020: 1-11.
[http://dx.doi.org/10.1155/2020/6263921] [PMID: 32587662]
[25]
Divi SN, Markova DZ, Fang T, et al. Circulating miR-155-5p as a novel biomarker of lumbar degenerative disc disease. Spine 2020; 45(9): E499-507.
[http://dx.doi.org/10.1097/BRS.0000000000003322] [PMID: 31770330]
[26]
Wang HQ, Yu XD, Liu ZH, et al. Deregulated miR-155 promotes Fas-mediated apoptosis in human intervertebral disc degeneration by targeting FADD and caspase-3. J Pathol 2011; 225(2): 232-42.
[http://dx.doi.org/10.1002/path.2931] [PMID: 21706480]
[27]
Han X, Huang C, Qu X, et al. Tripartite motif-containing 15 overexpression in non-small cell lung cancer is associated with poor patient prognoses. J Cancer 2019; 10(4): 843-52.
[http://dx.doi.org/10.7150/jca.27856] [PMID: 30854090]
[28]
Kudryashova E, Wu J, Havton LA, Spencer MJ. Deficiency of the E3 ubiquitin ligase TRIM32 in mice leads to a myopathy with a neurogenic component. Hum Mol Genet 2009; 18(7): 1353-67.
[http://dx.doi.org/10.1093/hmg/ddp036] [PMID: 19155210]
[29]
Chen F, Guo Q, Chen Q, et al. TRIM32 triggers β-catenin signaling through ubiquitylation of AXIN1 to promote inflammatory factor-induced apoptosis of rat nucleus pulposus cells. Am J Physiol Cell Physiol 2020; 318(3): C695-703.
[http://dx.doi.org/10.1152/ajpcell.00386.2019] [PMID: 31967859]
[30]
Fatima M, Kumari R, Schwamborn JC, et al. Tripartite containing motif 32 modulates proliferation of human neural precursor cells in HIV-1 neurodegeneration. Cell Death Differ 2016; 23(5): 776-86.
[http://dx.doi.org/10.1038/cdd.2015.138] [PMID: 26586575]
[31]
Liu L, Zhao X, Li P, et al. A novel way to isolate MSCs from umbilical cords. Eur J Immunol 2012; 42(8): 2190-3.
[http://dx.doi.org/10.1002/eji.201142356] [PMID: 22585466]
[32]
Liao ZW, Fan ZW, Huang Y, et al. Long non-coding RNA MT1DP interacts with miR-365 and induces apoptosis of nucleus pulposus cells by repressing NRF-2-induced anti-oxidation in lumbar disc herniation. Ann Transl Med 2021; 9(2): 151.
[http://dx.doi.org/10.21037/atm-20-8123] [PMID: 33569453]
[33]
Zhou S, Qiao Y, Liu Y, et al. Bone marrow derived mesenchymal stem cells pretreated with erythropoietin accelerate the repair of acute kidney injury. Cell Biosci 2020; 10(1): 130.
[http://dx.doi.org/10.1186/s13578-020-00492-2] [PMID: 33292452]
[34]
Hall SRR, Tsoyi K, Ith B, et al. Mesenchymal stromal cells improve survival during sepsis in the absence of heme oxygenase-1: The importance of neutrophils. Stem Cells 2013; 31(2): 397-407.
[http://dx.doi.org/10.1002/stem.1270] [PMID: 23132816]
[35]
Huang F, Gao T, Wang W, et al. Engineered basic fibroblast growth factor-overexpressing human umbilical cord-derived mesenchymal stem cells improve the proliferation and neuronal differentiation of endogenous neural stem cells and functional recovery of spinal cord injury by activating the PI3K-Akt-GSK-3β signaling pathway. Stem Cell Res Ther 2021; 12(1): 468.
[http://dx.doi.org/10.1186/s13287-021-02537-w] [PMID: 34419172]
[36]
Dong X, Bai X, Ni J, et al. Exosomes and breast cancer drug resistance. Cell Death Dis 2020; 11(11): 987.
[http://dx.doi.org/10.1038/s41419-020-03189-z] [PMID: 33203834]
[37]
Bian X, Ma K, Zhang C, Fu X. Therapeutic angiogenesis using stem cell-derived extracellular vesicles: An emerging approach for treatment of ischemic diseases. Stem Cell Res Ther 2019; 10(1): 158.
[http://dx.doi.org/10.1186/s13287-019-1276-z] [PMID: 31159859]
[38]
Xia C, Zeng Z, Fang B, et al. Mesenchymal stem cell-derived exosomes ameliorate intervertebral disc degeneration via anti-oxidant and anti-inflammatory effects. Free Radic Biol Med 2019; 143: 1-15.
[http://dx.doi.org/10.1016/j.freeradbiomed.2019.07.026] [PMID: 31351174]
[39]
Zhu L, Shi Y, Liu L, Wang H, Shen P, Yang H. Mesenchymal stem cells-derived exosomes ameliorate nucleus pulposus cells apoptosis via delivering miR-142-3p: Therapeutic potential for intervertebral disc degenerative diseases. Cell Cycle 2020; 19(14): 1727-39.
[http://dx.doi.org/10.1080/15384101.2020.1769301] [PMID: 32635856]
[40]
Wang CM, Cheng BH, Xue Q, Chen J, Bai B. MiR-1298 affects cell proliferation and apoptosis in C6 cells by targeting SET domain containing 7. Int J Immunopathol Pharmacol 2017; 30(3): 264-71.
[http://dx.doi.org/10.1177/0394632017720546] [PMID: 28762861]
[41]
Cai G, Qiao S, Chen K. Suppression of miR-221 inhibits glioma cells proliferation and invasion via targeting SEMA3B. Biol Res 2015; 48(1): 37.
[http://dx.doi.org/10.1186/s40659-015-0030-y] [PMID: 26197878]
[42]
Ma L, Xue H-B, Wang F, Shu C-M, Zhang J-H. MicroRNA-155 may be involved in the pathogenesis of atopic dermatitis by modulating the differentiation and function of T helper type 17 (Th17) cells. Clin Exp Immunol 2015; 181(1): 142-9.
[http://dx.doi.org/10.1111/cei.12624] [PMID: 25761610]
[43]
Johansson K, Malmhäll C, Ramos-Ramírez P, Rådinger M. MicroRNA-155 is a critical regulator of type 2 innate lymphoid cells and IL-33 signaling in experimental models of allergic airway inflammation. J Allergy Clin Immunol 2017; 139(3): 1007-1016.e9.
[http://dx.doi.org/10.1016/j.jaci.2016.06.035] [PMID: 27492144]
[44]
Ryu YS, Lee Y, Lee KW, et al. TRIM32 protein sensitizes cells to tumor necrosis factor (TNFα)-induced apoptosis via its RING domain-dependent E3 ligase activity against X-linked inhibitor of apoptosis (XIAP). J Biol Chem 2011; 286(29): 25729-38.
[http://dx.doi.org/10.1074/jbc.M111.241893] [PMID: 21628460]

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