Fig. 3: Systemic delivery of siMMP13<(EG18L)2 decreases PTOA-induced hyperalgesia and joint histopathology.
a, Schematic timeline for knee loading and treatment. Bilateral knee loading (3× per week, 5 weeks) was used to induce severe PTOA for comparing therapeutic impact of treatment with i.v. siMMP13<(EG18L)2, i.a. Zilretta, i.p. CL-82198 and i.p. Marimastat. b, Left: mechanical hyperalgesia was measured via algometer through day 35. Data over time displayed as mean + s.e.m. Right: AUC of average Smalgo readings over time was assessed. N = 8. c, Left: total MMP activity in mouse knees was measured using MMPsense 750 Fast (N = 8). Middle: mAbCII binding in knee joints was measured by fluorescence imaging (N = 8). Right: C2C fragments in mouse serum was measured by ELISA (N = 3). d, Knee joints were stained with toluidine blue (top row, femoral condyles shown) and H&E (bottom row, synovium lining and meniscus shown). Asterisks: white, healthy articular surface; red, loss of articular surface; yellow, healthy synovial lining/meniscus; black, synovial thickening/meniscal expansion and calcification. e, Joint cartilage damage was quantitated with the OARSI osteoarthritis cartilage histopathology assessment system (top) and DJD score (bottom). NS, not significant. In all panels, error bars indicate s.d. of biological replicates, unless specified otherwise.
