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

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. MSC-conditioned medium was prepared by stimulating primary human MSCs with tumour necrosis factor alpha (TNFα) and (50ng/ml each). Human synovium and cartilage explants were cultured in MSC-conditioned medium or in control medium, containing the same amount of added TNFα and IFNγ 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 (IκBa) was assessed by Western blot analysis. Synovial explants exposed to MSC-conditioned medium showed decreased gene expression of interleukin-1 beta (IL-1β), 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 IκBa was increased in synoviocytes and chondrocytes treated with MSC-conditioned medium. 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.

van Buul GM ，Villafuertes E ，Bos PK ，Waarsing JH ，Kops N ，Narcisi R ，Weinans H ，Verhaar JA ，Bernsen MR ，van Osch GJ ... -  《-》

Chondroprotective and anti-inflammatory effects of S-methylisothiourea, an inducible nitric oxide synthase inhibitor in cartilage and synovial explants model of osteoarthritis.

To study the chondroprotective and anti-inflammatory potential of inducible nitric oxide synthase (iNOS) inhibitor S-methylisothiourea (SMT) in in-vitro model. Rabbit cartilage explants were stimulated with recombinant human interleukin 1β (rhIL-1β), and the chondroprotective and anti-inflammatory effects of SMT were investigated. Rat synovial explants were stimulated with LPS, and the anti-inflammatory effect of SMT on synovium was studied. To examine the role of SMT in synovial inflammation mediated cartilage damage, LPS stimulated synovial explants were cultured with dead cartilage with or without SMT for 72 h. The culture medium was analysed for sulfated glycosaminoglycans (GAGs) and hydroxyproline as measure of proteoglycans and collagen degradation, respectively. SMT significantly reduced GAGs, hydroxyproline, matrix metalloproteinase (MMP)-13, tumour necrosis factor alpha (TNF-α), prostaglindin E2 (PGE2 ) and nitrite release in stimulated rabbit cartilage media indicating chondroprotective and anti-inflammatory effects of SMT in osteoarthritis (OA). Stimulated synovial explants caused release of nitrite, PGE2 , IL-1β and TNF-α in the medium which were significantly reduced by SMT indicating its anti-inflammatory action. SMT significantly reduced GAGs and hydroxyproline in medium and shown protective effect against synovium-mediated cartilage damage. SMT inhibited cartilage degradation, synovial inflammation and synovium-mediated cartilage damage, suggesting that SMT may be an agent for pharmacological intervention in OA.

Balaganur V ，Pathak NN ，Lingaraju MC ，More AS ，Latief N ，Kumari RR ，Kumar D ，Tandan SK ... -  《-》

Anti‑inflammatory and anti‑catabolic effect of non‑animal stabilized hyaluronic acid and mesenchymal stem cell‑conditioned medium in an osteoarthritis coculture model.

Simental-Mendía M ，Lozano-Sepúlveda SA ，Pérez-Silos V ，Fuentes-Mera L ，Martínez-Rodríguez HG ，Acosta-Olivo CA ，Peña-Martínez VM ，Vilchez-Cavazos F ... -  《-》

Effects of mesenchymal stem cells on interleukin-1β-treated chondrocytes and cartilage in a rat osteoarthritic model.

Tang J ，Cui W ，Song F ，Zhai C ，Hu H ，Zuo Q ，Fan W ... -  《-》

Human articular chondrocytes secrete parathyroid hormone-related protein and inhibit hypertrophy of mesenchymal stem cells in coculture during chondrogenesis.

Fischer J ，Dickhut A ，Rickert M ，Richter W ... -  《-》