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. 2022 Dec 1;28(12):2633–2645. doi: 10.1038/s41591-022-02059-9

Fig. 3. LNA043 treatment regenerates cartilage in rat OA and minipig cartilage injury models.

Fig. 3

a, Short-term rat OA model. Top left, schematic of the experimental design. i.a., intra-articular. Bottom left, representative images of knee joint sections from rats treated with vehicle or 20 μg LNA043 and stained with Safranin-O (red) or combined collagen type II (green) and X (red) IHC and counterstained with DAPI at 4 weeks post-RMT surgery. Scale bar, 200 μm. Right, cartilage damage, as determined by modified OARSI scoring (Supplementary Table 4) for naive (no surgery; n = 5), vehicle-treated (n = 9) and LNA043-treated rats (for 2 μg, n = 8; for 20 μg, n = 8; for 200 μg, n = 10). The data represent means ± s.d. Each data point represents the results from an individual rat. The percentage cartilage repair in LNA043-treated rats was calculated as the improvement in the score in vehicle-treated (0%) compared with naive rats (100%). Statistical significance was determined by Kruskal–Wallis non-parametric test with Dunn’s multiple comparison (*P = 0.279; **P = 0.0041). b, Therapeutic rat OA model. Top left, schematic of the experimental design. Bottom left, representative images of knee joint sections from rats treated with four weekly injections of vehicle or 400 μg LNA043 and stained with Safranin-O (red) 8 weeks post-meniscal tear surgery. Scale bar, 200 μm. The images to the right are magnifications of the sections highlighted by a dashed box to the left. Right, cartilage damage, as determined by modified OARSI scoring for naive, vehicle-treated and LNA043-treated rats (n = 10 per group). Data analysis and representation as in a (**P ≤ 0.0027). For a and b, the maximum cartilage damage score was 16. c, Minipig cartilage injury model. Top left, schematic of the experimental design. Bottom left, representative images of cartilage defect sites in trochlea stained with Safranin-O (red) at 12 months after two cycles of seven weekly/biweekly intra-articular injections of vehicle or 15 mg LNA043. The left and right images show the results from two different pigs. Scale bars, 700 μm. Right, cartilage quality was assessed macroscopically by the ICRS cartilage damage score (top and bottom left; Supplementary Table 5; 0 = normal; 20 = maximum damage), and cartilage repair was quantified in histopathology sections using a modified O’Driscoll cartilage repair score (top and bottom right; Supplementary Table 6; 21 = maximum repair), for vehicle-treated (n = 8) and LNA043-treated minipigs (n = 8) at 6 months (top) and vehicle-treated (n = 7) and LNA043-treated minipigs (n = 8) at 12 months (bottom). The data represent means ± s.e.m. Statistical significance was determined by two-tailed non-parametric Mann–Whitney U-test.