Fig. 5: Early-onset osteoarthritis in mice with deletion of genes differentially expressed in human osteoarthritis cartilage.

a 16-week-old mice with deletion of candidate genes differentially expressed in osteoarthritic human articular cartilage (Unk, Josd1, Gsdme, Arhgap30, Ccdc6, Col4a2, Mdb1, and Stau2) were investigated for osteoarthritis phenotypes. b Differential expression (log fold change, logFC) of human orthologues of candidate genes in low-grade versus high-grade osteoarthritis in human articular cartilage samples. Genes with significantly increased expression in high-grade osteoarthritis cartilage shown in green and those with decreased expression in red. c Iodine contrast-enhanced μCT images of lateral tibial plateau articular cartilage (red) and subchondral bone (blue) from wild-type (WT), Unk^−/−, Josd1^−/−, and Gsdme^−/− mice. Graphs show articular cartilage volume (Cg.V) and maximum articular cartilage thickness (Max Cg.Th) in Unk ^−/− (n = 4), Josd1^−/− (n = 6), and Gsdme^−/− (n = 4) mice. d Back-scattered electron-scanning electron microscopy images of tibial plateau joint surface replicas from WT, Unk^−/−, Josd1^−/−, and Gsdme^−/− mice. Graph shows articular cartilage (Cg) damage. e X-ray microradiography images of proximal tibia and the lateral tibial plateau subchondral bone region of interest (dashed box) from WT, Unk^−/−, Josd1^−/−, and Gsdme^−/− mice in which greyscale images are pseudocoloured according to a 16 color look-up table in which low bone mineral content (BMC) is yellow and high BMC is pink. Graph shows subchondral BMC (SC BMC Orange circles: individual mutant samples, black horizontal lines: sample mean. Gray boxes: reference ranges derived from 100 wild-type samples. For normally distributed parameters (Cg.V, Max. Cg.Th, SC BMC), reference range is two standard deviations above and below the mean (dashed line). For non-normally distributed parameters (Cg. Damage Area), reference range is the 2.5–97.5th percentile, and dashed line is the median. Scale bars = 100 μm (c, d) and 1 mm (e). *P < 0.00568, Bonferroni-corrected two-tailed Wilcoxon rank sum test. Cg.V: P = 0.00215 (Unk^−/−), Max. Cg.Th P = 0.00362 (Josd1^−/−), Cg. Damage Area: P = 0.00563 (Josd1^−/−), P = 0.00355 (Gsdme^−/−). mm millimeter. Source data are provided as a Source Data file.