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Desirable effect of combination therapy with high molecular weight hyaluronate and NSAIDs on MMP production M. Hashizume, M. Mihara Osteoarthritis and Cartilage Volume 17, Issue 11, Pages (November 2009) DOI: /j.joca Copyright © 2009 Osteoarthritis Research Society International Terms and Conditions
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Fig. 1 MMP levels in synovial lavage fluid from a rabbit OA model. OA-model rabbits were administered loxoprofen orally, with and without intra-articular injection of HA. Synovial lavage fluid was collected as described in Materials and methods. MMPs were measured by ELISA. Columns and error bars indicate the mean and SE of eight animals. Statistical significance was analyzed by the unpaired test and Dunnett's test (*P<0.05 vs control group, †P<0.05 vs NSAID group). Osteoarthritis and Cartilage , DOI: ( /j.joca ) Copyright © 2009 Osteoarthritis Research Society International Terms and Conditions
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Fig. 2 NSAIDs augmented cytokine-induced production of IL-1β and IL-6. Human chondrocytes were stimulated for 24h with IL-1β or IL-6/sIL-6R in the presence of an NSAID (CLE or IND) or DEX. After culture, the concentration of IL-1β or IL-6 in the supernatant was determined by ELISA. “None” indicates nothing was added, “Control” indicates that only IL-1β or IL-6/sIL-6R was added. Columns and error bars indicate the mean and SD of triplicate cultures. Statistical significance was analyzed by Dunnett's test (*P<0.05 vs control). Osteoarthritis and Cartilage , DOI: ( /j.joca ) Copyright © 2009 Osteoarthritis Research Society International Terms and Conditions
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Fig. 3 HA inhibited the IL-6/sIL-6R- and IL-1β-induced production of MMP. Human chondrocytes were stimulated for 24h (A) with IL-6/sIL-6R in the presence of anti-IL-6 receptor antibody (tocilizumab, 100μg/mL) or HA (0.01, 0.1, 1mg/mL) and (B) with IL-1β in the presence of an IL-1 receptor antagonist (IL-1Ra, 50μg/mL) or HA (1mg/mL). “None”, “Control”, columns and error bars as in Fig. 2. Statistical significance was analyzed by Dunnett's test (*P<0.05 vs none, †P<0.05 vs control). Osteoarthritis and Cartilage , DOI: ( /j.joca ) Copyright © 2009 Osteoarthritis Research Society International Terms and Conditions
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Fig. 4 HA inhibited the NSAID-induced augmentation of MMP and IL-6 production. Human chondrocytes were stimulated for 24h with IL-6/sIL-6R in the presence of an NSAID (1000nM CEL or 100nM IND) with and without HA. After culture, the concentrations of MMPs and IL-6 in the supernatant were determined by ELISA. “Control” indicates that only IL-6/sIL-6R was added. Columns and error bars indicate the mean and SD of triplicate cultures. Statistical significance was analyzed by Dunnett's test (†P<0.05 vs NSAID+IL-6/sIL-6R). Osteoarthritis and Cartilage , DOI: ( /j.joca ) Copyright © 2009 Osteoarthritis Research Society International Terms and Conditions
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Fig. 5 HA inhibited the NSAID-induced augmentation of MMP and IL-1β production. Human chondrocytes were cultured as in Fig. 4, but stimulated with IL-1β instead of IL-6/sIL-6R. After culture, the concentrations of MMPs and IL-1β in the supernatant were determined by ELISA. “Control” indicates that only IL-1â was added. Columns and error bars indicate the mean and SD of triplicate cultures. Statistical significance was analyzed by Dunnett's test (†P<0.05 vs NSAID+IL-1β). Osteoarthritis and Cartilage , DOI: ( /j.joca ) Copyright © 2009 Osteoarthritis Research Society International Terms and Conditions
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