Thrombospondin-1 Partly Mediates the Cartilage Protective Effect of Adipose-Derived Mesenchymal Stem Cells in Osteoarthritis
ObjectiveAssuming that mesenchymal stem cells (MSCs) respond to the osteoarthritic joint environment to exert a chondroprotective effect, we aimed at investigating the molecular response setup by MSCs after priming by osteoarthritic chondrocytes in cocultures.MethodsWe used primary human osteoarthri...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01638/full |
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| author | Marie Maumus Marie Maumus Cristina Manferdini Karine Toupet Karine Toupet Paul Chuchana Paul Chuchana Louis Casteilla Mélanie Gachet Mélanie Gachet Christian Jorgensen Christian Jorgensen Christian Jorgensen Gina Lisignoli Danièle Noël Danièle Noël Danièle Noël |
| author_facet | Marie Maumus Marie Maumus Cristina Manferdini Karine Toupet Karine Toupet Paul Chuchana Paul Chuchana Louis Casteilla Mélanie Gachet Mélanie Gachet Christian Jorgensen Christian Jorgensen Christian Jorgensen Gina Lisignoli Danièle Noël Danièle Noël Danièle Noël |
| author_sort | Marie Maumus |
| collection | DOAJ |
| description | ObjectiveAssuming that mesenchymal stem cells (MSCs) respond to the osteoarthritic joint environment to exert a chondroprotective effect, we aimed at investigating the molecular response setup by MSCs after priming by osteoarthritic chondrocytes in cocultures.MethodsWe used primary human osteoarthritic chondrocytes and adipose stem cells (ASCs) in mono- and cocultures and performed a high-throughput secretome analysis. Among secreted proteins differentially induced in cocultures, we identified thrombospondin-1 (THBS1) as a potential candidate that could be involved in the chondroprotective effect of ASCs.ResultsSecretome analysis revealed significant induction of THBS1 in ASCs/chondrocytes cocultures at mRNA and protein levels. We showed that THBS1 was upregulated at late stages of MSC differentiation toward chondrocytes and that recombinant THBS1 (rTHBS1) exerted a prochondrogenic effect on MSC indicating a role of THBS1 during chondrogenesis. However, compared to control ASCs, siTHBS1-transfected ASCs did not decrease the expression of hypertrophic and inflammatory markers in osteoarthritic chondrocytes, suggesting that THBS1 was not involved in the reversion of osteoarthritic phenotype. Nevertheless, downregulation of THBS1 in ASCs reduced their immunosuppressive activity, which was consistent with the anti-inflammatory role of rTHBS1 on T lymphocytes. THBS1 function was then evaluated in the collagenase-induced OA model by comparing siTHBS1-transfected and control ASCs. The protective effect of ASCs evaluated by histological and histomorphological analysis of cartilage and bone was not seen with siTHBS1-transfected ASCs.ConclusionOur data suggest that THBS1 did not exert a direct protective effect on chondrocytes but might reduce inflammation, subsequently explaining the therapeutic effect of ASCs in OA. |
| first_indexed | 2024-12-16T18:01:51Z |
| format | Article |
| id | doaj.art-b7278f61b7514de28cb9fedd8c91ba0d |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-16T18:01:51Z |
| publishDate | 2017-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-b7278f61b7514de28cb9fedd8c91ba0d2022-12-21T22:22:02ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-11-01810.3389/fimmu.2017.01638297037Thrombospondin-1 Partly Mediates the Cartilage Protective Effect of Adipose-Derived Mesenchymal Stem Cells in OsteoarthritisMarie Maumus0Marie Maumus1Cristina Manferdini2Karine Toupet3Karine Toupet4Paul Chuchana5Paul Chuchana6Louis Casteilla7Mélanie Gachet8Mélanie Gachet9Christian Jorgensen10Christian Jorgensen11Christian Jorgensen12Gina Lisignoli13Danièle Noël14Danièle Noël15Danièle Noël16INSERM, U1183, Hôpital Saint-Eloi, Montpellier, FranceMontpellier University, UFR de Médecine, Montpellier, FranceSC Laboratorio di Immunoreumatologia e Rigenerazione Tissutale, Istituto Ortopedico Rizzoli, Bologna, ItalyINSERM, U1183, Hôpital Saint-Eloi, Montpellier, FranceMontpellier University, UFR de Médecine, Montpellier, FranceINSERM, U1183, Hôpital Saint-Eloi, Montpellier, FranceMontpellier University, UFR de Médecine, Montpellier, FranceUMR STROMALab, CNRS 5273, INSERM U1031, Université Toulouse III-Paul Sabatier, Toulouse, FranceINSERM, U1183, Hôpital Saint-Eloi, Montpellier, FranceMontpellier University, UFR de Médecine, Montpellier, FranceINSERM, U1183, Hôpital Saint-Eloi, Montpellier, FranceMontpellier University, UFR de Médecine, Montpellier, FranceClinical Immunology and Osteoarticular Diseases Therapeutic Unit, Hôpital Lapeyronie, Montpellier, FranceSC Laboratorio di Immunoreumatologia e Rigenerazione Tissutale, Istituto Ortopedico Rizzoli, Bologna, ItalyINSERM, U1183, Hôpital Saint-Eloi, Montpellier, FranceMontpellier University, UFR de Médecine, Montpellier, FranceClinical Immunology and Osteoarticular Diseases Therapeutic Unit, Hôpital Lapeyronie, Montpellier, FranceObjectiveAssuming that mesenchymal stem cells (MSCs) respond to the osteoarthritic joint environment to exert a chondroprotective effect, we aimed at investigating the molecular response setup by MSCs after priming by osteoarthritic chondrocytes in cocultures.MethodsWe used primary human osteoarthritic chondrocytes and adipose stem cells (ASCs) in mono- and cocultures and performed a high-throughput secretome analysis. Among secreted proteins differentially induced in cocultures, we identified thrombospondin-1 (THBS1) as a potential candidate that could be involved in the chondroprotective effect of ASCs.ResultsSecretome analysis revealed significant induction of THBS1 in ASCs/chondrocytes cocultures at mRNA and protein levels. We showed that THBS1 was upregulated at late stages of MSC differentiation toward chondrocytes and that recombinant THBS1 (rTHBS1) exerted a prochondrogenic effect on MSC indicating a role of THBS1 during chondrogenesis. However, compared to control ASCs, siTHBS1-transfected ASCs did not decrease the expression of hypertrophic and inflammatory markers in osteoarthritic chondrocytes, suggesting that THBS1 was not involved in the reversion of osteoarthritic phenotype. Nevertheless, downregulation of THBS1 in ASCs reduced their immunosuppressive activity, which was consistent with the anti-inflammatory role of rTHBS1 on T lymphocytes. THBS1 function was then evaluated in the collagenase-induced OA model by comparing siTHBS1-transfected and control ASCs. The protective effect of ASCs evaluated by histological and histomorphological analysis of cartilage and bone was not seen with siTHBS1-transfected ASCs.ConclusionOur data suggest that THBS1 did not exert a direct protective effect on chondrocytes but might reduce inflammation, subsequently explaining the therapeutic effect of ASCs in OA.http://journal.frontiersin.org/article/10.3389/fimmu.2017.01638/fullmesenchymal stem cellstrophic factorsthrombospondincell therapyosteoarthritischondrogenesis |
| spellingShingle | Marie Maumus Marie Maumus Cristina Manferdini Karine Toupet Karine Toupet Paul Chuchana Paul Chuchana Louis Casteilla Mélanie Gachet Mélanie Gachet Christian Jorgensen Christian Jorgensen Christian Jorgensen Gina Lisignoli Danièle Noël Danièle Noël Danièle Noël Thrombospondin-1 Partly Mediates the Cartilage Protective Effect of Adipose-Derived Mesenchymal Stem Cells in Osteoarthritis Frontiers in Immunology mesenchymal stem cells trophic factors thrombospondin cell therapy osteoarthritis chondrogenesis |
| title | Thrombospondin-1 Partly Mediates the Cartilage Protective Effect of Adipose-Derived Mesenchymal Stem Cells in Osteoarthritis |
| title_full | Thrombospondin-1 Partly Mediates the Cartilage Protective Effect of Adipose-Derived Mesenchymal Stem Cells in Osteoarthritis |
| title_fullStr | Thrombospondin-1 Partly Mediates the Cartilage Protective Effect of Adipose-Derived Mesenchymal Stem Cells in Osteoarthritis |
| title_full_unstemmed | Thrombospondin-1 Partly Mediates the Cartilage Protective Effect of Adipose-Derived Mesenchymal Stem Cells in Osteoarthritis |
| title_short | Thrombospondin-1 Partly Mediates the Cartilage Protective Effect of Adipose-Derived Mesenchymal Stem Cells in Osteoarthritis |
| title_sort | thrombospondin 1 partly mediates the cartilage protective effect of adipose derived mesenchymal stem cells in osteoarthritis |
| topic | mesenchymal stem cells trophic factors thrombospondin cell therapy osteoarthritis chondrogenesis |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01638/full |
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