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

Slides:

Advertisements

Similar presentations

Pro-inflammatory stimulation of meniscus cells increases production of matrix metalloproteinases and additional catabolic factors involved in osteoarthritis.

Advertisements

Multiple injections of platelet rich plasma releasate reduce pain and synovial thickening in a mice osteoarthritis model S. Khatab, G.M. van Buul, P.K.

A potential role of chondroitin sulfate on bone in osteoarthritis: inhibition of prostaglandin E2 and matrix metalloproteinases synthesis in interleukin-1β-

MicroRNA-558 regulates the expression of cyclooxygenase-2 and IL-1β-induced catabolic effects in human articular chondrocytes S.J. Park, E.J. Cheon,

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is increased in osteoarthritis and regulates chondrocyte catabolic and anabolic activities

Pressure and inflammatory stimulation induced increase of cadherin-11 is mediated by PI3K/Akt pathway in synovial fibroblasts from temporomandibular joint

A statistical model of shape and density of the proximal femur in relation to radiological and clinical OA of the hip J.H. Waarsing, R.M. Rozendaal,

L. Pesesse, C. Sanchez, D. A. Walsh, J. -P. Delcour, C. Baudouin, P

A new player in cartilage homeostasis: adiponectin induces nitric oxide synthase type II and pro-inflammatory cytokines in chondrocytes R. Lago, B.S.,

B. J. E. de Lange-Brokaar, A. Ioan-Facsinay, G. J. V. M. van Osch, A

M. -H. Moon, J. -K. Jeong, Y. -J. Lee, J. -W. Seol, C. J. Jackson, S

Mesenchymal stromal cells for cartilage repair in osteoarthritis

TGFβ inhibition during expansion phase increases the chondrogenic re-differentiation capacity of human articular chondrocytes R. Narcisi, L. Signorile,

Guiding synovial inflammation by macrophage phenotype modulation: an in vitro study towards a therapy for osteoarthritis L. Utomo, G.J.V.M. van Osch,

Cannabinoid WIN-55,212-2 mesylate inhibits interleukin-1β induced matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase expression.

Long-term NSAID treatment directly decreases COX-2 and mPGES-1 production in the articular cartilage of patients with osteoarthritis M.A. Álvarez-Soria,

Immunomodulatory effect of mesenchymal stem cells following intra-articular injection in a model of osteoarthritis: a potential role for apoptosis P.

Human osteoarthritic synovium impacts chondrogenic differentiation of mesenchymal stem cells via macrophage polarisation state N. Fahy, M.L. de Vries-van.

L. Raymond, S. Eck, E. Hays, I. Tomek, M. D. , S. Kantor, M. D. , M

MicroRNA-558 regulates the expression of cyclooxygenase-2 and IL-1β-induced catabolic effects in human articular chondrocytes S.J. Park, E.J. Cheon,

Histone deacetylase inhibitors suppress interleukin-1β-induced nitric oxide and prostaglandin E2 production in human chondrocytes N. Chabane, M.Sc.,

The chondroprotective effect of selective COX-2 inhibition in osteoarthritis: ex vivo evaluation of human cartilage tissue after in vivo treatment T.N.

Anti-apoptotic effect of transforming growth factor-β1 on human articular chondrocytes: role of protein phosphatase 2A M. Lires-Deán, B.S., B. Caramés,

Aging-related inflammation in osteoarthritis

Expression and function of the insulin receptor in normal and osteoarthritic human chondrocytes: modulation of anabolic gene expression, glucose transport.

MicroRNA-320 regulates matrix metalloproteinase-13 expression in chondrogenesis and interleukin-1β-induced chondrocyte responses F. Meng, Z. Zhang, W.

Pro-inflammatory stimulation of meniscus cells increases production of matrix metalloproteinases and additional catabolic factors involved in osteoarthritis.

P. -J. Francin, A. Abot, C. Guillaume, D. Moulin, A. Bianchi, P

P38 MAPK inhibition selectively mitigates inflammatory mediators and VEGF production in AF cells co-cultured with activated macrophage-like THP-1 cells

Α-MSH inhibits TNF-α-induced matrix metalloproteinase-13 expression by modulating p38 kinase and nuclear factor κB signaling in human chondrosarcoma HTB-94.

Glucosamine promotes chondrogenic phenotype in both chondrocytes and mesenchymal stem cells and inhibits MMP-13 expression and matrix degradation A.

Expression and regulation of Toll-like receptor 2 by IL-1β and fibronectin fragments in human articular chondrocytes S.-L. Su, M.S., C.-D. Tsai, Ph.D.,

Adipose stromal cells mediated switching of the pro-inflammatory profile of M1-like macrophages is facilitated by PGE2: in vitro evaluation C. Manferdini,

Glucosamine reduces anabolic as well as catabolic processes in bovine chondrocytes cultured in alginate E.J. Uitterlinden, M.D., H. Jahr, Ph.D., J.L.M.

Molecular Therapy - Nucleic Acids

E. Farrell, P. Wielopolski, P. Pavljasevic, N. Kops, H. Weinans, M. R

DIO2 modifies inflammatory responses in chondrocytes

Immunomodulatory effect of mesenchymal stem cells following intra-articular injection in a model of osteoarthritis: a potential role for apoptosis P.

Calcitonin directly attenuates collagen type II degradation by inhibition of matrix metalloproteinase expression and activity in articular chondrocytes

Resistin is elevated following traumatic joint injury and causes matrix degradation and release of inflammatory cytokines from articular cartilage in.

Inflammatory stimuli differentially modulate the transcription of paracrine signaling molecules of equine bone marrow multipotent mesenchymal stromal.

M. Cucchiarini, H. Madry, E.F. Terwilliger

B. J. E. de Lange-Brokaar, A. Ioan-Facsinay, G. J. V. M. van Osch, A

N.D. Miljkovic, M.D., Ph.D., G.M. Cooper, Ph.D., K.G. Marra, Ph.D.

T. Kurth, M. Sc. , E. Hedbom, Ph. D. , N. Shintani, Ph. D. , M

Biochemical and functional modulation of the cartilage collagen network by IGF1, TGFβ2 and FGF2 Y.M. Jenniskens, M.Sc., W. Koevoet, B.Sc., A.C.W. de.

Stage-specific differences in secretory profile of mesenchymal stromal cells (MSCs) subjected to early- vs late-stage OA synovial fluid A. Gómez-Aristizábal,

Implication of prostaglandin E2 in TNF-α-induced release of m-calpain from HCS-2/8 chondrocytes. Inhibition of m-calpain release by NSAIDs K. Fushimi,

Inhibition of ADAMTS-7 and ADAMTS-12 degradation of cartilage oligomeric matrix protein by alpha-2-macroglobulin Y. Luan, Ph.D., M.D., L. Kong, Ph.D.,

Mevastatin reduces cartilage degradation in rabbit experimental osteoarthritis through inhibition of synovial inflammation Y. Akasaki, M.D., S. Matsuda,

Multiple injections of platelet rich plasma releasate reduce pain and synovial thickening in a mice osteoarthritis model S. Khatab, G.M. van Buul, P.K.

Osteoarthritis and Cartilage

M. Durigova, M.Sc., P.J. Roughley, Ph.D., J.S. Mort, Ph.D.

Safety of intra-articular cell-therapy with culture-expanded stem cells in humans: a systematic literature review C.M.M. Peeters, M.J.C. Leijs, M. Reijman,

Arthritic and non-arthritic synovial fluids modulate IL10 and IL1RA gene expression in differentially activated primary human monocytes S. Lopa, M.J.C.

In vitro release of corticosteroids in a new model of slow release platform in the treatment of osteoarthritis. S. Colen, M. van Rijen, S. Plomp, L.

Chondroitin sulfate modulation of matrix and inflammatory gene expression in IL-1β- stimulated chondrocytes – study in hypoxic alginate bead cultures

Y. M. Bastiaansen-Jenniskens, M. Sc. , W. Koevoet, B. Sc. , A. C. W

Differential regulation of proteoglycan 4 metabolism in cartilage by IL-1α, IGF-I, and TGF-β1 T.A. Schmidt, Ph.D., N.S. Gastelum, B.S., E.H. Han, M.S.,

A peptide temporally enhanced chondrogenesis of mesenchymal stem cells

Endurable injectable mesenchymal stem cell therapy for osteoarthritis by encapsulation in alginate constructs M.J. Leijs, G.M. van Buul, M.F. Nieboer,

Novel juvenile factors for cartilage regeneration

Cellular origin of neocartilage formed at wound edges of articular cartilage in a tissue culture experiment P.K. Bos, M.D., Ph.D., N. Kops, B.Sc., J.A.N.

R. H. J. Das, M. Sc. , H. Jahr, Ph. D. , J. A. N. Verhaar, M. D. , Ph

Osteoarthritis year 2012 in review: biology

Contribution of calcium-containing crystals to cartilage degradation and synovial inflammation in osteoarthritis Y.Z. Liu, A.P. Jackson, S.D. Cosgrove

Insulin decreases autophagy and leads to cartilage degradation

Y. Akasaki, A. Hasegawa, M. Saito, H. Asahara, Y. Iwamoto, M.K. Lotz

Peroxisome proliferator activated receptor alpha activation decreases inflammatory and destructive responses in osteoarthritic cartilage S. Clockaerts,

Arthritic synovial fluid influences expression of pro- and anti-inflammatory mediators in macrophages S. Lopa, M. Leijs, M. Moretti, E. Lubberts, G.

Presentation transcript:

Mesenchymal stem cells secrete factors that inhibit inflammatory processes in short- term osteoarthritic synovium and cartilage explant culture G.M. van Buul, E. Villafuertes, P.K. Bos, J.H. Waarsing, N. Kops, R. Narcisi, H. Weinans, J.A.N. Verhaar, M.R. Bernsen, G.J.V.M. van Osch Osteoarthritis and Cartilage Volume 20, Issue 10, Pages 1186-1196 (October 2012) DOI: 10.1016/j.joca.2012.06.003 Copyright © 2012 OsteoArthritis Society International Terms and Conditions

Fig. 1 Influence of TNFα/IFNγ stimulation on MSC gene expression (A) and MSC secretions (B). In order to stimulate the immunomodulatory capacity, MSCs were treated with TNFα and IFNγ for 24h. Media from TNFα/IFNγ stimulated and unstimulated MSCs were analyzed for various factors and corrected for control medium containing 10% FCS. Gene expression data are presented as boxplots for four experiments performed in triplicate. Cell secretion data are presented as means±standard deviations for three experiments performed in triplicate. *P<0.05; **P<0.01; ***P<0.005. Osteoarthritis and Cartilage 2012 20, 1186-1196DOI: (10.1016/j.joca.2012.06.003) Copyright © 2012 OsteoArthritis Society International Terms and Conditions

Fig. 2 Effects of factors secreted by non-stimulated MSCs on expression of genes related to inflammation and matrix degradation in human osteoarthritic synovial explants. Data are presented as boxplots for three experiments, in which MSC-conditioned medium from three MSC donors was applied to triplicate explants from three OA donors; explants were treated for 48h. Osteoarthritis and Cartilage 2012 20, 1186-1196DOI: (10.1016/j.joca.2012.06.003) Copyright © 2012 OsteoArthritis Society International Terms and Conditions

Fig. 3 Effects of factors secreted by non-stimulated MSCs on expression of genes related to inflammation and matrix degradation in human osteoarthritic cartilage explants. Data are presented as boxplots for three experiments, in which MSC-conditioned medium from three MSC donors was applied to triplicate explants from three OA donors; explants were treated for 48h. Osteoarthritis and Cartilage 2012 20, 1186-1196DOI: (10.1016/j.joca.2012.06.003) Copyright © 2012 OsteoArthritis Society International Terms and Conditions

Fig. 4 Effects of factors secreted by TNFα/IFNγ stimulated MSCs on expression of genes related to inflammation and matrix degradation in human osteoarthritic synovial explants. Data are presented as boxplots for five experiments, in which MSC-conditioned medium from five MSC donors was applied to triplicate explants from five OA donors; explants were treated for 48h; *P<0.05; **P<0.01; ***P<0.005. Osteoarthritis and Cartilage 2012 20, 1186-1196DOI: (10.1016/j.joca.2012.06.003) Copyright © 2012 OsteoArthritis Society International Terms and Conditions

Fig. 5 Effects of factors secreted by TNFα/IFNγ stimulated MSCs on expression of genes related to inflammation and matrix turnover in human osteoarthritic cartilage explants. Data are presented as boxplots for five experiments, in which MSC-conditioned medium from five MSC donors was applied to triplicate explants from five OA donors; explants were treated for 48h; ***P<0.005. Osteoarthritis and Cartilage 2012 20, 1186-1196DOI: (10.1016/j.joca.2012.06.003) Copyright © 2012 OsteoArthritis Society International Terms and Conditions

Fig. 6 Influence of factors secreted by TNFα/IFNγ stimulated MSCs on NO (A) and PGE2 secretion (B) by synovium (left panels) and cartilage (right panels) explants. Data are presented as boxplots for five experiments (NO) or four experiments (PGE2), in which MSC-conditioned medium from five MSC donors was applied to triplicate explants from five, respectively four, OA donors. Regarding NO measurements, all triplicate samples were measured individually; regarding PGE2 measurements, triplicates were pooled and measured in duplicate. Explants were treated for 48h; **P<0.01. Osteoarthritis and Cartilage 2012 20, 1186-1196DOI: (10.1016/j.joca.2012.06.003) Copyright © 2012 OsteoArthritis Society International Terms and Conditions

Fig. 7 Influence of factors secreted by TNFα/IFNγ stimulated MSCs on p38 MAP kinase phosphorylation (A) and IκBa presence (B) in both synoviocytes and chondrocytes was measured by Western blot. Presence of IκBa was increased in both cell-types by MSC-conditioned medium, thereby indicating an inhibitory effect on NFκB activation. Data are presented as means±standard deviations for single values obtained in two experiments; cells were treated for 3h for p38 MAP kinase evaluation or 10min for IκBa analysis. Osteoarthritis and Cartilage 2012 20, 1186-1196DOI: (10.1016/j.joca.2012.06.003) Copyright © 2012 OsteoArthritis Society International Terms and Conditions

Fig. S1 The paracrine effects of TNFα/IFNγ stimulated MSCs were determined in synovium and cartilage co-culture, a model resembling more closely the in vivo situation. The MSC secretome modified expression of genes related to inflammation and matrix turnover in synovium (A) and cartilage (B). This experiment was performed as confirmation of previously performed experiments using separate synovium and cartilage explants. Data are presented as means±standard deviations for one experiment performed in triplicate with pooled MSC-conditioned medium of five donors; explants were treated for 48h. Osteoarthritis and Cartilage 2012 20, 1186-1196DOI: (10.1016/j.joca.2012.06.003) Copyright © 2012 OsteoArthritis Society International Terms and Conditions

Fig. S2 To evaluate whether the TNFα/IFNγ model reflected pathological OA processes, we tested the effects of TNFα/IFNγ on synovial explants from three donors. Data are presented as boxplots for three experiments performed in triplicate; explants were treated for 48h; ***P<0.005. Osteoarthritis and Cartilage 2012 20, 1186-1196DOI: (10.1016/j.joca.2012.06.003) Copyright © 2012 OsteoArthritis Society International Terms and Conditions

Fig. S3 Effects of TNFα/IFNγ on OA cartilage explants. Data are presented as boxplots for three experiments performed in triplicate; explants were treated for 48h; *P<0.05; **P<0.01; ***P<0.005. Osteoarthritis and Cartilage 2012 20, 1186-1196DOI: (10.1016/j.joca.2012.06.003) Copyright © 2012 OsteoArthritis Society International Terms and Conditions