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. 2015 Aug 18;75(6):1246–1254. doi: 10.1136/annrheumdis-2014-207203

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This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/

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Effect of AR786 on MIA-induced or MNX-induced knee inflammation. Small changes in knee diameter were observed after intra-articular injection of MIA or saline (A), or after MNX surgery or sham surgery (B), as indicated by small differences between injected/operated and contralateral knees. Either AR786 (30 mg/kg twice daily) or vehicle (5% Gelucire) control was administered orally from day 14 (treatment). Knee diameters did not differ significantly between MIA-injected or saline-injected knees, nor between MIA-injected rats treated with either AR786 or vehicle (A). Knee diameter differences between operated and contralateral, non-operated knees were greater in MNX-operated than in sham-operated rats from 14 days after surgery (B). Differences in knee diameter between AR786-treated and vehicle-treated, MNX-operated rats at day 21 (7 days after the start of treatment) did not reach statistical significance. Synovitis scores, determined by histology, were significantly higher for MIA-injected rats (C) at 21 days and MNX-operated rats (D) at 28 days compared with saline-injected or sham-operated controls. Synovitis scores were reduced in MIA-injected rats following treatment for 7 days with oral AR786 compared with Gelucire vehicle-treated controls (C). Synovitis scores were not inhibited by preventive administration of AR786 in MNX-operated rats (D). Data are median of n=10 rats/group (A and B). Significance of post hoc tests is denoted by the number of symbols, for example, *p<0.05; **p<0.01; ***p<0.001. Asterisks (*) denote differences from saline-injected or sham-operated, vehicle-treated control rats. Hash sign (#) denotes differences from MIA-injected rats that received AR786. In (D), MNX-operated, AR786-treated rats either continued to receive AR786 until the end of the experiment at day 28 (AR786+), or AR786 treatment was discontinued and replaced by vehicle treatment from day 14 (AR786−). No significant differences were observed between continued and discontinued treatment groups. MIA, monosodium-iodoacetate; MNX, meniscal transection.