Exosomes Derived from Bone Marrow Mesenchymal Stem Cells Prevent Acidic pH-Induced Damage in Human Nucleus Pulposus Cells.

Ming Li, Ruoyu Li, Sidong Yang, Dalong Yang, Xianda Gao, Jiayuan Sun, Wenyuan Ding, Lei Ma
Author Information
  1. Ming Li: Department of Spine Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China (mainland).
  2. Ruoyu Li: Department of Spine Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China (mainland).
  3. Sidong Yang: Department of Spine Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China (mainland).
  4. Dalong Yang: Department of Spine Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China (mainland).
  5. Xianda Gao: Department of Spine Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China (mainland).
  6. Jiayuan Sun: Department of Spine Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China (mainland).
  7. Wenyuan Ding: Department of Spine Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China (mainland).
  8. Lei Ma: Department of Spine Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China (mainland).

Abstract

BACKGROUND The exosomes (Exo) derived from mesenchymal stem cells (MSCs) are capable of attenuating the apoptosis of nucleus pulposus cells (NPCs) elicited by proinflammatory cytokines. However, it remains unknown whether MSC-derived Exo also exert a protective effect on NPCs in the pathological acid environment. MATERIAL AND METHODS NPCs were divided into 3 groups: Group A, pH 7.1-7.3; Group B, pH 6.5-6.7 and Group C, pH 5.9-6.1. The NPCs were cultured in the above-defined acidic medium, and 3 different amounts of Exo were added into the media. Finally, the expression of the caspase-3, aggrecan, collagen II, and MMP-13 was analyzed and compared among the different groups. RESULTS Compared with cells cultured at pH 7.1-7.3 (Group A), proliferation activity of NPCs cultured at pH 5.9-6.7 (Group B and C) decreased significantly. Collagen II and aggrecan expression was also obviously reduced with the decrease of cell proliferation. Conversely, the expression of caspase-3 and MMP-13 significantly increased. Further experiments showed that proliferation activity was significantly attenuated in NPCs cultured at pH 5.9-6.1 without Exo treatment (Group E) compared with those cultured at pH 7.1-7.3 without Exo treatment (Group D). CONCLUSIONS In the pathological acid environment, MSC-derived Exo promotes the expression of chondrocyte extracellular matrix, collagen II, and aggrecan, and reduces matrix degradation by downregulating matrix-degrading enzymes, protecting NPCs from acidic pH-induced apoptosis. This study reveals a promising strategy for treatment of IVD degeneration.

References

  1. Biores Open Access. 2018 Feb 01;7(1):2-9 [PMID: 29445584]
  2. Stem Cells Dev. 2015 Nov 1;24(21):2479-95 [PMID: 26228642]
  3. Spine (Phila Pa 1976). 2006 Aug 15;31(18):2151-61 [PMID: 16915105]
  4. Stem Cell Rev Rep. 2015 Feb;11(1):150-60 [PMID: 25091427]
  5. FASEB J. 2019 Jul;33(7):8055-8068 [PMID: 30964699]
  6. Arch Med Sci. 2012 Dec 20;8(6):952-6 [PMID: 23319966]
  7. Sci Rep. 2016 Nov 17;6:37360 [PMID: 27853274]
  8. Connect Tissue Res. 2014 Jun;55(3):197-204 [PMID: 24432912]
  9. Biosci Rep. 2018 Nov 13;38(6): [PMID: 30291218]
  10. J Orthop Res. 2010 May;28(5):623-30 [PMID: 19953600]
  11. Methods. 2016 Apr 15;99:69-80 [PMID: 26384579]
  12. Stem Cells Int. 2012;2012:921053 [PMID: 22550520]
  13. Biochem Biophys Res Commun. 2015 May 22;461(1):76-9 [PMID: 25849885]
  14. Annu Rev Physiol. 2015;77:13-27 [PMID: 25293529]
  15. Lancet. 2016 Oct 8;388(10053):1545-1602 [PMID: 27733282]
  16. Biochim Biophys Acta Mol Basis Dis. 2018 Nov;1864(11):3754-3768 [PMID: 30251693]
  17. J Cell Physiol. 2019 Nov;234(11):20310-20321 [PMID: 30997693]
  18. Spine J. 2013 Mar;13(3):352-62 [PMID: 23340343]
  19. Stem Cells Dev. 2019 Jun 15;28(12):799-811 [PMID: 30896296]
  20. Spine J. 2010 Sep;10(9):802-10 [PMID: 20655810]
  21. Acta Orthop Scand. 1969;40(1):23-42 [PMID: 4312806]
  22. Transplantation. 2011 Oct 15;92(7):822-8 [PMID: 21792091]
  23. J Cell Mol Med. 2018 Jan;22(1):261-276 [PMID: 28805297]
  24. J Cell Physiol. 2019 Nov;234(11):19977-19989 [PMID: 30945295]
  25. Spine (Phila Pa 1976). 1992 Sep;17(9):1079-82 [PMID: 1411761]
  26. Arthritis Res Ther. 2014 Oct 08;16(5):457 [PMID: 25293819]
  27. Spine (Phila Pa 1976). 2008 Aug 1;33(17):1843-9 [PMID: 18670337]
  28. Osteoarthritis Cartilage. 2015 Jul;23(7):1057-70 [PMID: 25827971]
  29. J Med Invest. 2016;63(1-2):1-7 [PMID: 27040045]
  30. Osteoarthritis Cartilage. 2014 Jul;22(7):1053-60 [PMID: 24857972]
  31. Stem Cell Res Ther. 2017 May 10;8(1):108 [PMID: 28486958]
  32. Curr Stem Cell Res Ther. 2019;14(1):57-64 [PMID: 30227822]
  33. Biochem Biophys Res Commun. 2009 Feb 20;379(4):824-9 [PMID: 19133233]
  34. Osteoarthritis Cartilage. 2016 Feb;24(2):206-12 [PMID: 26342641]

MeSH Term

Aggrecans
Apoptosis
Cell Proliferation
Cells, Cultured
Chondrocytes
Collagen Type II
Exosomes
Extracellular Matrix
Humans
Hydrogen-Ion Concentration
Intervertebral Disc
Intervertebral Disc Degeneration
Mesenchymal Stem Cells
Nucleus Pulposus

Chemicals

Aggrecans
Collagen Type II

Word Cloud

Created with Highcharts 10.0.0NPCsGrouppHExo37culturedexpressioncells1-759-6aggrecanIIproliferationsignificantlytreatmentapoptosisMSC-derivedalsopathologicalacidenvironmentBC1acidicdifferentcaspase-3collagenMMP-13comparedactivitywithoutmatrixCellsBACKGROUNDexosomesderivedmesenchymalstemMSCscapableattenuatingnucleuspulposuselicitedproinflammatorycytokinesHoweverremainsunknownwhetherexertprotectiveeffectMATERIALANDMETHODSdividedgroups:65-6above-definedmediumamountsaddedmediaFinallyanalyzedamonggroupsRESULTSCompareddecreasedCollagenobviouslyreduceddecreasecellConverselyincreasedexperimentsshowedattenuatedEDCONCLUSIONSpromoteschondrocyteextracellularreducesdegradationdownregulatingmatrix-degradingenzymesprotectingpH-inducedstudyrevealspromisingstrategyIVDdegenerationExosomesDerivedBoneMarrowMesenchymalStemPreventAcidicpH-InducedDamageHumanNucleusPulposus

Similar Articles

Cited By