Characterization of the Proteins Secreted by Equine Muscle-Derived Mesenchymal Stem Cells Exposed to Cartilage Explants in Osteoarthritis Model.
Cartilage explant
Decorin
Equine mesenchymal stem cells
Matrix metalloproteinase 3 (mmp3)
Osteoarthritis
SILAC
Secreted proteins
Journal
Stem cell reviews and reports
ISSN: 2629-3277
Titre abrégé: Stem Cell Rev Rep
Pays: United States
ID NLM: 101752767
Informations de publication
Date de publication:
02 2023
02 2023
Historique:
accepted:
06
10
2022
pubmed:
23
10
2022
medline:
9
2
2023
entrez:
22
10
2022
Statut:
ppublish
Résumé
Osteoarthritis (OA) is a highly prevalent joint degenerative disease for which therapeutic treatments are limited or invasive. Cell therapy based on mesenchymal stem/stromal cells (MSCs) is therefore seen as a promising approach for this disease, in both human and horses. As the regenerative potential of MSCs is mainly conferred by paracrine function, the goal of this study was to characterize the secreted proteins of muscle-derived MSCs (mdMSCs) in an in vitro model of OA to evaluate the putative clinical interest of mdMSCs as cell therapy for joint diseases like osteoarthritis. An equine osteoarthritis model composed of cartilage explants exposed to pro-inflammatory cytokines was first developed. Then, the effects of mdMSC co-culture on cartilage explant were studied by measuring the glycosaminoglycan release and the NO Co-culture with muscle-derived MSCs decreases the cytokine-induced glycosaminoglycan release by cartilage explants, suggesting a protecting effect of mdMSCs. Among the 52 equine proteins sequenced in the co-culture conditioned medium, the abundance of decorin and matrix metalloproteinase 3 was significantly modified, as confirmed by western blot analyses. These results suggest that muscle-derived MSCs could reduce the catabolic effect of TNFα and IL-1β on cartilage explant by decreasing the secretion and activity of matrix metalloproteinase 3 and increasing the decorin secretion. mdMSCs capacity to reduce the catabolic consequences of cartilage exposure to pro-inflammatory cytokines. These effects can be explained by mdMSC-secreted bioactive such as TIMP-1 and decorin, known as an inhibitor of MMP3 and an anti-inflammatory protein, respectively.
Sections du résumé
BACKGROUND
Osteoarthritis (OA) is a highly prevalent joint degenerative disease for which therapeutic treatments are limited or invasive. Cell therapy based on mesenchymal stem/stromal cells (MSCs) is therefore seen as a promising approach for this disease, in both human and horses. As the regenerative potential of MSCs is mainly conferred by paracrine function, the goal of this study was to characterize the secreted proteins of muscle-derived MSCs (mdMSCs) in an in vitro model of OA to evaluate the putative clinical interest of mdMSCs as cell therapy for joint diseases like osteoarthritis.
METHODS
An equine osteoarthritis model composed of cartilage explants exposed to pro-inflammatory cytokines was first developed. Then, the effects of mdMSC co-culture on cartilage explant were studied by measuring the glycosaminoglycan release and the NO
RESULTS
Co-culture with muscle-derived MSCs decreases the cytokine-induced glycosaminoglycan release by cartilage explants, suggesting a protecting effect of mdMSCs. Among the 52 equine proteins sequenced in the co-culture conditioned medium, the abundance of decorin and matrix metalloproteinase 3 was significantly modified, as confirmed by western blot analyses.
CONCLUSIONS
These results suggest that muscle-derived MSCs could reduce the catabolic effect of TNFα and IL-1β on cartilage explant by decreasing the secretion and activity of matrix metalloproteinase 3 and increasing the decorin secretion. mdMSCs capacity to reduce the catabolic consequences of cartilage exposure to pro-inflammatory cytokines. These effects can be explained by mdMSC-secreted bioactive such as TIMP-1 and decorin, known as an inhibitor of MMP3 and an anti-inflammatory protein, respectively.
Identifiants
pubmed: 36271312
doi: 10.1007/s12015-022-10463-4
pii: 10.1007/s12015-022-10463-4
pmc: PMC9902419
doi:
Substances chimiques
Cytokines
0
Decorin
0
Glycosaminoglycans
0
Matrix Metalloproteinase 3
EC 3.4.24.17
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
550-567Informations de copyright
© 2022. The Author(s).
Références
J Orthop Res. 2021 May;39(5):1017-1029
pubmed: 32725904
Osteoarthritis Cartilage. 2012 Oct;20(10):1147-51
pubmed: 22781206
Inflammopharmacology. 2018 Oct;26(5):1207-1217
pubmed: 29460078
J Biol Chem. 1991 Feb 5;266(4):2017-20
pubmed: 1846608
J Orthop Res. 2018 Mar;36(3):823-831
pubmed: 28921609
Disabil Rehabil. 2008;30(20-22):1752-8
pubmed: 18608378
J Proteomics. 2012 Jun 27;75(12):3720-32
pubmed: 22575385
J Rheumatol. 1999 Sep;26(9):2002-14
pubmed: 10493683
Biomed Pharmacother. 2019 Jan;109:2318-2326
pubmed: 30551490
Cell Mol Life Sci. 2019 Sep;76(17):3323-3348
pubmed: 31055643
Int J Mol Sci. 2017 Apr 25;18(5):
pubmed: 28441353
Cell Tissue Res. 2017 Oct;370(1):53-70
pubmed: 28413859
Adv Exp Med Biol. 2022;1401:23-55
pubmed: 35733035
Cells. 2019 Aug 03;8(8):
pubmed: 31382623
Stem Cell Res Ther. 2020 May 20;11(1):187
pubmed: 32434555
Front Bioeng Biotechnol. 2019 Dec 17;7:411
pubmed: 31921815
J Proteomics. 2017 Aug 23;166:115-126
pubmed: 28739509
BMC Vet Res. 2016 Nov 8;12(1):246
pubmed: 27821120
Biomaterials. 2007 Dec;28(36):5401-6
pubmed: 17915311
Arthritis Res Ther. 2014 May 09;16(3):R110
pubmed: 24886698
Int J Mol Sci. 2021 Mar 05;22(5):
pubmed: 33807695
Exp Mol Med. 2013 Nov 15;45:e54
pubmed: 24232253
J Biochem. 1998 Mar;123(3):431-9
pubmed: 9538225
Int J Mol Sci. 2020 Sep 03;21(17):
pubmed: 32899238
Cold Spring Harb Perspect Biol. 2018 May 1;10(5):
pubmed: 28507020
Front Immunol. 2019 May 16;10:1112
pubmed: 31164890
Front Pharmacol. 2022 Jul 15;13:861183
pubmed: 35910349
Nat Protoc. 2006;1(6):2650-60
pubmed: 17406521
Osteoarthritis Cartilage. 2008;16 Suppl 2:S15-20
pubmed: 18794013
Mol Med Rep. 2020 May;21(5):2243-2250
pubmed: 32323772
Cells. 2020 May 28;9(6):
pubmed: 32481562
Biomaterials. 2005 Aug;26(22):4540-9
pubmed: 15722123
BMC Musculoskelet Disord. 2020 Feb 14;21(1):99
pubmed: 32059658
Stem Cell Res Ther. 2011 Feb 23;2(1):9
pubmed: 21371354
J Cell Biol. 1966 Mar;28(3):473-87
pubmed: 4163861
BMC Vet Res. 2019 Oct 22;15(1):358
pubmed: 31640767
Front Bioeng Biotechnol. 2021 Dec 21;9:787020
pubmed: 34993189
Int J Mol Sci. 2019 Sep 27;20(19):
pubmed: 31569732
J Proteome Res. 2020 Sep 4;19(9):3652-3667
pubmed: 32701294
Arthritis Rheum. 2007 Jan;56(1):147-57
pubmed: 17195217
Int Immunopharmacol. 2009 Feb;9(2):230-40
pubmed: 19100343
Life Sci. 2019 Oct 1;234:116786
pubmed: 31445934
Clin Proteomics. 2019 Jul 18;16:32
pubmed: 31360146
Animals (Basel). 2021 Mar 25;11(4):
pubmed: 33805967
Mol Cell Proteomics. 2018 Dec;17(12):2534-2545
pubmed: 30385480
J Knee Surg. 2018 Oct;31(9):834-840
pubmed: 29294496
Clinics (Sao Paulo). 2011;66(8):1431-6
pubmed: 21915496
J Biol Chem. 2008 Feb 22;283(8):4850-65
pubmed: 18065760
Dis Model Mech. 2015 Jan;8(1):17-30
pubmed: 25561745
Biochem Biophys Res Commun. 2004 Mar 26;316(1):182-8
pubmed: 15003528
Matrix Biol. 2018 Oct;71-72:51-69
pubmed: 29803938
Ther Adv Cardiovasc Dis. 2011 Dec;5(6):305-14
pubmed: 22089475
Nat Protoc. 2016 Apr;11(4):795-812
pubmed: 27010757
Clin Immunol. 2013 Mar;146(3):185-96
pubmed: 23360836
Cytokine Growth Factor Rev. 2018 Oct;43:25-37
pubmed: 29954665
Sci Rep. 2019 Feb 28;9(1):3096
pubmed: 30816242
Biomaterials. 2020 Jan;226:119544
pubmed: 31648137
Infect Immun. 2003 Mar;71(3):1442-52
pubmed: 12595462
Stem Cells Int. 2018 Jun 6;2018:5340756
pubmed: 29977307
Sci Rep. 2017 Apr 6;7(1):696
pubmed: 28386120
Equine Vet J. 2020 Sep;52(5):654-663
pubmed: 31971273
Tissue Eng Part A. 2009 Jul;15(7):1739-49
pubmed: 19119922
J Orthop Res. 2018 Sep;36(9):2431-2438
pubmed: 29704279
Mol Cell Proteomics. 2002 May;1(5):376-86
pubmed: 12118079
Clin Transl Med. 2018 Nov 21;7(1):36
pubmed: 30460596
Methods Enzymol. 1983;101:582-98
pubmed: 6888276
Osteoarthritis Cartilage. 2017 Aug;25(8):1199-1209
pubmed: 28232143
Cold Spring Harb Symp Quant Biol. 1988;53 Pt 2:789-98
pubmed: 3076097
Mol Cell Biol. 1990 May;10(5):2327-34
pubmed: 2183031
Osteoarthritis Cartilage. 2005 Feb;13(2):162-70
pubmed: 15694578
Res Vet Sci. 2018 Jun;118:317-323
pubmed: 29601969
Rheumatology (Oxford). 2020 Oct 1;59(10):2681-2694
pubmed: 32691066
Nucleic Acids Res. 2022 Jan 7;50(D1):D543-D552
pubmed: 34723319
Stem Cells Transl Med. 2017 Dec;6(12):2173-2185
pubmed: 29076267
Osteoarthritis Cartilage. 2019 Feb;27(2):230-239
pubmed: 30391394
J Neurosci Res. 2003 Dec 15;74(6):801-6
pubmed: 14648584
Bioorg Med Chem. 2021 May 15;38:116132
pubmed: 33872958
Front Mol Biosci. 2022 Jul 26;9:942729
pubmed: 35959462
Stem Cell Res Ther. 2019 Nov 21;10(1):340
pubmed: 31753036
Cells. 2020 Jun 11;9(6):
pubmed: 32545382
Arthritis Rheum. 2009 Oct;60(10):2985-96
pubmed: 19790045
J Proteomics. 2011 May 1;74(5):704-15
pubmed: 21354348
Curr Rheumatol Rep. 2019 Jun 15;21(8):38
pubmed: 31203465
Am J Sports Med. 2005 Nov;33(11):1647-53
pubmed: 16093540
Front Immunol. 2018 Dec 04;9:2837
pubmed: 30564236
Biochimie. 2013 Dec;95(12):2196-211
pubmed: 23880644
Vet Pathol. 2015 Sep;52(5):803-18
pubmed: 26063173