AUTHOR=Maumus Marie , Manferdini Cristina , Toupet Karine , Chuchana Paul , Casteilla Louis , Gachet Mélanie , Jorgensen Christian , Lisignoli Gina , Noël Danièle 

TITLE=Thrombospondin-1 Partly Mediates the Cartilage Protective Effect of Adipose-Derived Mesenchymal Stem Cells in Osteoarthritis

JOURNAL=Frontiers in Immunology

VOLUME=Volume 8 - 2017

YEAR=2017

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.01638

DOI=10.3389/fimmu.2017.01638

ISSN=1664-3224

ABSTRACT=Objective: Assuming that mesenchymal stem cells respond to the osteoarthritic (OA) joint environment to exert a chondroprotective effect, we aimed at investigating the molecular response set up by MSCs after priming by OA chondrocytes in cocultures. 
Methods: We used primary human OA 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.
Results: Secretome analysis revealed significant induction of THBS1 in ASCs/chondrocytes cocultures at mRNA and protein levels. We showed that THBS1 was up-regulated at late stages of MSC differentiation towards chondrocytes and that recombinant THBS1 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 OA chondrocytes, suggesting that THBS1 was not involved in the reversion of OA phenotype. Nevertheless, down-regulation of THBS1 in ASCs reduced their immunosuppressive activity, which was consistent with the anti-inflammatory role of recombinant THBS1 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. 
Conclusion: Our 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.