Fig 1.
Pain behaviour in the traditional versus modified DMM model of OA.
Adult male C57BL/6 mice underwent either traditional destabilisation of the medial meniscus (DMM) (n = 9) or sham surgery (n = 8) (A) and weight bearing asymmetry was measured up to 16 weeks post model induction. Adult male C57BL/6 mice underwent either modified destabilisation of the medial meniscus (DMM) (n = 16) or sham surgery (n = 18) (B) and weight bearing asymmetry was measured up to 16 weeks post model induction. Data analysed by 2-way ANOVA with Bonferroni corrected multiple corrections. * = p<0.05, ** = p<0.01 DMM vs Sham. Differences in the area under the curve of weight-bearing asymmetry 12 to 16 weeks following traditional or modified DMM surgeries (C) was analysed by Kruskal-Wallis test with Dunn’s multiple comparisons. * = p<0.05, ** = p<0.01 when compared to traditional DMM.
Fig 2.
Pathology in the traditional versus modified DMM model of OA.
Adult male C57BL/6 mice underwent either traditional destabilisation of the medial meniscus (DMM) (n = 7) or sham surgery (n = 6) (A, B, C, D). Cartilage damage (A) and synovitis (B) were analysed 16 weeks post-surgery. Representative images of sham (C) and traditional DMM (D) joints. Adult male C57BL/6 mice underwent either modified destabilisation of the medial meniscus (DMM) (n = 8) or sham surgery (n = 8) (E, F, G, H). Cartilage damage (E) and synovitis (F) were analysed 16 weeks post-surgery. Representative images of sham (G) and modified DMM (H) joints. Data analysed by Mann Whitney U-Test ** = p<0.01 DMM vs Sham.
Fig 3.
Pain behaviour and joint pathology are not correlated in the traditional or modified DMM models in the mouse.
Adult male C57BL/6 mice underwent traditional destabilisation of the medial meniscus (DMM) (n = 9) (A,B). Weight bearing asymmetry at 16 weeks post model induction was not correlated with either cartilage damage (A) or synovitis (B). Adult male C57BL/6 mice underwent modified DMM (n = 16) (C,D). Weight bearing asymmetry at 16 weeks post-modified DMM was not correlated with either cartilage damage (C) and synovitis (D). Data analysed Spearman’s rho.
Fig 4.
No effect of modified DMM surgery on pain behavior up to 20 weeks post-surgery.
(A) Adult male C57BL/6 mice underwent either modified destabilisation of the medial meniscus (DMM) (n = 16) or sham surgery (n = 8) and weight bearing asymmetry was measured up to 20 weeks post model induction. Data analysed by 2-way ANOVA with Bonferroni corrected multiple corrections. * = p<0.05. (B) Cartilage damage and (C) synovitis were analysed 20 weeks post-surgery. Data analysed by Mann Whitney U Test, ** = p<0.01 DMM vs Sham.
Fig 5.
Quantification of neuroimmune cell activation in the dorsal horn of the spinal cord.
Adult male C57BL/6 mice underwent traditional DMM, modified DMM, or sham surgery. Dorsal horn spinal cord Iba-1 immunostaining for microglia and GFAP immunofluorescence for astrocytes was quantified at 16 weeks after surgery. (A) Quantification of Iba-1 immunostaining in mice that underwent traditional DMM (n = 8) or sham surgery (n = 6). (B) Quantification of IBA1 immunostaining in mice that underwent modified DMM (n = 8) or sham surgery (n = 6). Data are reported as average number of activated microglia in the ipsilateral and contralateral dorsal horn. (C) Representative images of Iba-1 staining in the dorsal horn of the spinal cord. Data were analysed by Kruskal-Wallis test with Dunn’s multiple comparisons, no significant differences observed. GFAP immunofluorescence data are the average sum grey intensity value measured using Velocity software. (D) Quantification of GFAP immunostaining in mice that underwent traditional DMM (n = 8) or sham surgery (n = 6). (E) Quantification of GFAP immunostaining in mice that underwent modified DMM (n = 8) or sham surgery (n = 6). (F) Representative images of GFAP immunostaining in the superficial dorsal horn of mice that underwent traditional or modified DMM surgery. Data were analysed by one-way ANOVA with a Dunnett’s multiple comparison, no significant differences observed.
Fig 6.
Pain behaviour in the modified MNX model of OA in the rat.
Adult Sprague Dawley Rats underwent either modified MNX surgery (n = 11) or sham surgery (n = 9). Weight bearing asymmetry (A) and paw withdrawal thresholds (B) was measured up to 16 weeks post model induction. Data analysed by 2-way ANOVA with Bonferroni corrected multiple corrections. * = p<0.05, ** = p<0.01, *** = p<0.001, **** = p<0.0001 MMNX vs Sham.
Fig 7.
Joint pathology changes 16 weeks following induction of the modified MNX rat model of OA pain.
Adult male Sprague Dawley rats underwent either modified MNX or sham surgery. Cartilage damage (A), synovitis (B), and osteophytes (C) were analysed 16 weeks post-surgery. Data analysed by Mann Whitney U test. ** = p<0.01, *** = p<0.001, **** = p<0.0001 MMNX vs Sham.
Fig 8.
Time-course of joint pathology changes in the modified MNX model in the rat.
Adult male Sprague Dawley rats underwent either modified MNX or sham surgery. Cartilage damage (A), synovitis (B), and osteophytes (C) were analysed 4 (n = 8 per group), 8 (n = 8 per group), 12 (n = 8 per group) and 16 (n = 8 per group) weeks post-surgery. Data analysed by one-way ANOVA with Bonferroni’s corrected multiple comparisons ** = p<0.01, *** = p<0.001, **** = p<0.0001 MMNX vs Sham. Representative images (20x) of the medial tibial plateau highlight the progression of cartilage damage in this model (D).