Mesenchymal stem cells secrete factors that inhibit inflammatory processes in short-term osteoarthritic synovium and cartilage explant culture

Objective: Mesenchymal stem cells (MSCs) are promising candidates for osteoarthritis (OA) therapies, although their mechanism of action remains unclear. MSCs have recently been discovered to secrete anti-inflammatory cytokines and growth factors. We studied the paracrine effects of MSCs on OA cartilage and synovial explants in vitro. Design: MSC-conditioned medium was prepared by stimulating primary human MSCs with tumour necrosis factor alpha (TNF alpha) and (50 ng/ml each). Human synovium and cartilage explants were cultured in MSC-conditioned medium or in control medium, containing the same amount of added TNF alpha and IFN gamma but not incubated with MSCs. Explants were analyzed for gene expression and the production of nitric oxide (NO). The presence of the inhibitor of nuclear factor kappa B alpha (I kappa Ba) was assessed by Western blot analysis. Results: Synovial explants exposed to MSC-conditioned medium showed decreased gene expression of interleukin-1 beta (IL-1 beta), matrix metalloproteinase (MMP)1 and MMP13, while suppressor of cytokine signaling (SOCS)1 was upregulated. In cartilage, expression of IL-1 receptor antagonist (IL-1RA) was upregulated, whereas a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)5 and collagen type II alpha 1 (COL2A1) were downregulated. MSC-conditioned medium reduced NO production in cartilage explants and the presence of I kappa Ba was increased in synoviocytes and chondrocytes treated with MSC-conditioned medium. Conclusions: In an inflammatory environment. MSCs secrete factors which cause multiple anti-inflammatory effects and influence matrix turnover in synovium and cartilage explants. Thereby, the presented data encourage further study of MSCs as a treatment for joint diseases. (C) 2012 OsteoArthritis Society International. Published by Elsevier Ltd. All rights reserved.