Extended Data Fig. 3: Systemic (i.v.) siMMP13<(EG18L)2 (10 mg/kg) treatment achieves long-term retention and MMP13 silencing in PTOA knee joints.
a, Timeline for mouse left knee mechanical loading (3 times / week) and single treatment (day 0; 7 days after initiation of mechanical loading) with Cy5-siRNA<(EG18L)2 or siMMP13<(EG18L)2. b, Cryosection confocal microscopy imaging of Cy5-siRNA<(EG18L)2 in joint tissues taken down on day 1 post-treatment. c-e, Cy5-siRNA<(EG18L)2 was visualized on day 30 post-treatment by confocal microscopy of knee joint cryosections (c, representative images with dashed lines outlining articular cartilage), and at time points from 0-30 days post-treatment by longitudinal intravital Cy5 imaging (d). Semiquantitative analysis of the AUC (Cy5 fluorescence x days) was calculated (e) (N = 4). f-g, Knee joint Mmp13 was measured at the indicated time points by qRT-PCR (e) and IHC (f) in healthy or PTOA knee tissues collected at the indicated time points from mice treated with or without siMMP13<(EG18L)2. N = 5-6. For all panels: Error bars indicate standard deviation of biological replicates. Knees labeled healthy indicate a non-loaded contralateral limb (right).
