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

Autor: Harrie Weinans, E. Villafuertes, Pieter K. Bos, G.J.V.M. van Osch, Roberto Narcisi, Monique R. Bernsen, Jan A N Verhaar, Nicole Kops, G.M. van Buul, Jan H. Waarsing
Přispěvatelé: Radiology & Nuclear Medicine, Orthopedics and Sports Medicine, Otorhinolaryngology and Head and Neck Surgery
Rok vydání: 2012
Předmět:
Cartilage
Articular
medicine.medical_treatment
Immune modulation
Interleukin-1beta
Biomedical Engineering
Gene Expression
Suppressor of Cytokine Signaling Proteins
Osteoarthritis
Matrix metalloproteinase
Nitric Oxide
MSC
Interferon-gamma
Paracrine signalling
Chondrocytes
Suppressor of Cytokine Signaling 1 Protein
NF-KappaB Inhibitor alpha
Rheumatology
SDG 3 - Good Health and Well-being
Matrix Metalloproteinase 13
medicine
Humans
Orthopedics and Sports Medicine
OA
Cells
Cultured
Mesenchymal stem cell
Tumor Necrosis Factor-alpha
Chemistry
Cartilage
ADAMTS
Synovial Membrane
Mesenchymal Stem Cells
medicine.disease
Coculture Techniques
medicine.anatomical_structure
Cytokine
Paracrine
Culture Media
Conditioned
Immunology
Collagen
type II
alpha 1
Cancer research
I-kappa B Proteins
Matrix Metalloproteinase 1
Chondrogenesis
Biomarkers
Zdroj: Osteoarthritis and Cartilage, 20(10), 1186-1196. W.B. Saunders
ISSN: 1063-4584
Popis: Summary 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 (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. Results 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. 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.
Databáze: OpenAIRE
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