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

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Resistin is elevated following traumatic joint injury and causes matrix degradation and release of inflammatory cytokines from articular cartilage in vitro J.H. Lee, T. Ort, K. Ma, K. Picha, J. Carton, P.A. Marsters, L.S. Lohmander, F. Baribaud, X.-Y.R. Song, S. Blake Osteoarthritis and Cartilage Volume 17, Issue 5, Pages 613-620 (May 2009) DOI: 10.1016/j.joca.2008.08.007 Copyright © 2008 Osteoarthritis Research Society International Terms and Conditions

Fig. 1 Resistin levels in SF (A) and serum (B) samples from patients taken at different times since posttraumatic joint injury. Time intervals were chosen to produce an approximately equal number of samples in each group (n=29–43 in each interval). The data presented in box and whiskers plots where the line across the middle of the box is the median, the limits of the box are the 25th and 75th percentiles The “whiskers” extending above and below the box end at the most extreme data point that is no more than 1.5 times the interquartile range away from the ends of the box. Any data points beyond this are displayed as circles. The highest resistin values in both SF and serum were observed at shorter time points – up to 5 weeks after injury. Osteoarthritis and Cartilage 2009 17, 613-620DOI: (10.1016/j.joca.2008.08.007) Copyright © 2008 Osteoarthritis Research Society International Terms and Conditions

Fig. 2 IHC staining of synovium (A, B) and cartilage (C, D) tissues from normal (A, C) and OA (B, D) patients with an anti-resistin antibody. The arrows indicate examples of the cells positively stained with anti-resistin antibody. Magnification is 40×. The images are representative of sections taken from three patients. Osteoarthritis and Cartilage 2009 17, 613-620DOI: (10.1016/j.joca.2008.08.007) Copyright © 2008 Osteoarthritis Research Society International Terms and Conditions

Fig. 3 Human monocytes from two donors were treated with recombinant human resistin for 48h and resistin-stimulated (A) IL-6, (B) CXCL8/IL-8 and (C) CCL2/MCP-1 release were assayed by human multiplex cytokine kit. Each sample was run in duplicate. Results are presented as mean (pg/ml)±SD, * indicates P-value<0.05 by Dunnett's test. Osteoarthritis and Cartilage 2009 17, 613-620DOI: (10.1016/j.joca.2008.08.007) Copyright © 2008 Osteoarthritis Research Society International Terms and Conditions

Fig. 4 Mouse articular cartilage was cultured in conditioned media from resistin-treated monocytes. An increase in the release of s-GAG was measured in the media following 3 days of culture using the DMMB assay. Results are presented as mean±SE, n=4; * indicates P-value<0.05 by Dunnett's test. Osteoarthritis and Cartilage 2009 17, 613-620DOI: (10.1016/j.joca.2008.08.007) Copyright © 2008 Osteoarthritis Research Society International Terms and Conditions

Fig. 5 Mouse articular cartilage was treated with human recombinant resistin for 3 days. (A) Culture supernatants were assayed for s-GAG content by the DMMB dye assay. Results presented are mean±SE, n=4; * indicates P-value<0.05 in individual pairwise comparisons of each active group vs the control using Dunnett's test. Control (B, D) and 10μg/ml resistin-treated (C, E) cartilage explants were fixed for histology and stained with Toluidine Blue to visualize loss of proteoglycans. Magnification is 10× (B, C) and 40× (D, E). The arrows indicate decreased staining intensity of the cartilage matrix in the periphery of the tissue explants. Osteoarthritis and Cartilage 2009 17, 613-620DOI: (10.1016/j.joca.2008.08.007) Copyright © 2008 Osteoarthritis Research Society International Terms and Conditions

Fig. 6 Mouse cartilage explants were treated with different concentrations of recombinant human resistin for 3 days. Resistin-stimulated secretion of IL-6, CCL2/JE, CXCL8/KC (A) and (B) PGE2 was measured by Luminex or ELISA kit, respectively. Results presented are mean±SE, n=4; * indicates P-value<0.05 in individual pairwise comparisons of each active group vs the control using Dunnett's test. Osteoarthritis and Cartilage 2009 17, 613-620DOI: (10.1016/j.joca.2008.08.007) Copyright © 2008 Osteoarthritis Research Society International Terms and Conditions

Fig. 7 Human articular cartilage explants isolated from a non-OA donor were treated with recombinant human resistin for 14 days. Proteoglycan synthesis was measured by [35S]-sulfate incorporation during the last 16h of treatment. The explants isolated from a second non-OA donor showed similar inhibition in proteoglycan synthesis in response to resistin treatment. Results presented are mean±SE, n=6; * indicates P-value<0.05 in individual pairwise comparisons of each active group vs the control using Dunnett's test. Osteoarthritis and Cartilage 2009 17, 613-620DOI: (10.1016/j.joca.2008.08.007) Copyright © 2008 Osteoarthritis Research Society International Terms and Conditions