Fig. 4: Intravenous delivery of siMMP13<(EG18L)2 achieves multijoint accumulation, MMP13 knockdown and diminished arthritis progression in a mouse RA model.
a,b, In a mouse inflammatory arthritis (K/BxN serum transfer) model, mice were treated with Cy5-siRNA<(EG18L)2, Cy5-siRNA-Chol and Cy5-siRNA (1 mg kg−1 i.v.) 4 days after receiving K/BxN serum transfer. Joints of forepaw, hindpaw and knee were collected 24 h later and assessed by IVIS imaging (a) or fluorescence microscopy of hindpaw ankle joints (b). Representative images and quantitation of IVIS data are shown. N = 6. Dashed lines outline articular cartilage in fluorescence microscopy images of tissue cryosections. c, Relative Mmp13 mRNA in forepaws, knees and hindpaws of healthy untreated wild-type mice or in K/BxN serum recipients treated with siControl<(EG18L)2 or siMMP13<(EG18L)2 (10 mg kg−1 i.v.) was measured by RT–qPCR. N = 6. Error bars represent s.d. of biological replicates. d–f, K/BxN serum recipients were treated with siMMP13<(EG18L)2, methylprednisolone or CL-82198 (10 mg kg−1). d, Schematic timeline for K/BxN serum transfer and treatment. e, Photos of hindpaws were collected on treatment day 10, and representative images are shown. f, Ankle width change, clinical score, algometer ankle joint hyperalgesia and severity index were measured for 10 days after treatment. Error bars indicate s.e.m. (top) or s.d. (bottom) of biological replicates.
