RNA interference-based silencing of Plekho1 with osteoblast-selective delivery alleviates articular inflammation and inhibits bone erosion in non-human primate arthritis model induced by type II bovine collagen. (a) Body weight monitoring over time of each cynomolgus monkey after treatment. (b) Analysis of arthritis score over time of each cynomolgus monkey after treatment. (c) PIP joints swelling monitoring over time of each cynomolgus monkey after treatment. (d) Representative histological change of PIP joints from the hand of cynomolgus monkey in each group (four PIPs in each cynomolgus monkey, three cynomolgus monkeys in each group). Scale bar, 500 μm. (e) Comparison of histological inflammation score in each group. (f) Radiological score monitoring over time by X ray examination of the hand in each cynomolgus monkey. (g) Representative X ray image of the hand in each group (three cynomolgus monkeys in each group). (h) Representative 3D microarchitecture of the PIP in each group (four PIPs in each cynomolgus monkey, three cynomolgus monkeys in each group), obtained by microCT examination. Scale bars, 1.0 mm. (i) Analysis of the three-dimensional architecture parameters (BMD and BV/TV) for monkeys in each group. (j) Bone formation was examined by sequential labels with fluorescent dye in nondecalcified bone sections from cynomolgus monkeys. Representative fluorescent micrographs of PIP showed the xylenol (red) and calcein (green) labels in each group (four PIPs in each cynomolgus monkey, three cynomolgus monkeys in each group). Scale bar, 10 μm. (k) Analysis of bone histomorphometric parameters (MAR and BFR/BS) from cynomolgus monkeys in each group. All data are the mean ± s.d. *P < 0.05. A one-way ANOVA with subsequent Tukey's multiple comparisons test was performed. Note: CIA-BL, collagen-induced arthritis baseline; NS, (AspSerSer)6-liposome -NS siRNA; siRNA, (AspSerSer)6- liposome -Plekho1 siRNA; TB, treatment begins; PIP, proximal interphalangeal. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)