Fig. 5: Deletion of osteocyte transcriptome signature genes affects bone structure and function. | Nature Communications

Fig. 5: Deletion of osteocyte transcriptome signature genes affects bone structure and function.

From: Osteocyte transcriptome mapping identifies a molecular landscape controlling skeletal homeostasis and susceptibility to skeletal disease

Fig. 5: Deletion of osteocyte transcriptome signature genes affects bone structure and function.

a The 26 osteocyte transcriptome signature genes with outlier skeletal phenotypes in the Origins of Bone and Cartilage Disease (OBCD) database of single gene deletions in mice (outer ring). Deletion of genes in blue affected bone structure, genes in brown affected bone function and genes in red both structure and function. Those annotated in either GO or MGI are indicated. Genes in red have a significant outlier phenotype when deleted in knockout mice but are not annotated with skeletal function or phenotype in either GO or MGI databases. The inner ring denotes the number of genes with (green) and without (grey) an outlier skeletal phenotype when deleted in mice in the OBCD database. b Representative quantitative X-ray microradiographic images from the femurs (i) and vertebrae (ii) of adult, female wild-type (WT), Auts2+/−, Cttnbp2−/−, Dact3−/− and Ldlrad4−/− mice (n = 6 mice per genotype). Scale bar = 1 mm. Dot plots illustrate individual parameters. c Representative micro-CT images of trabecular (i) and cortical (ii) bone of adult, female wild-type (WT), Auts2+/−, Cttnbp2−/−, Dact3−/− and Ldlrad4−/− mice (n = 6 mice per genotype). Scale bar = 100 µm. Dot plots illustrate bone volume as a proportion of tissue volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), cortical thickness (Ct.Th), internal endosteal diameter and bone mineral density (BMD). d Representative micro-CT images showing large osteocyte lacunae (401–800 µm3) in tibia cortical bone from adult, female WT (n = 11), Auts2+/− (n = 6), Cttnbp2−/− (n = 6), Dact3−/− (n = 6) and Ldlrad4−/− (n = 4) mice. Scale bar = 100 μm. Graphs show osteocyte lacunae number per bone volume (Lc.N/BV) and distribution of lacunae volumes (Lc.V) in WT mice (median and 95% confidence intervals). Violin plot shows distribution of Lc.V in the four knockout mouse lines compared to WT and graphs show relative frequency distribution of Lc.V in Cttnbp2−/− and Ldlrad4−/− mice compared to WT. Kruskall–Wallis test followed by Dunn’s multiple comparison adjustment (two-sided) **P < 0.01, ****P < 0.0001. e Load displacement curves from caudal vertebrae compression testing in adult female WT, Auts2+/−, Cttnbp2−/−, Dact3−/− and Ldlrad4−/− mice. Dot plots show yield load, maximum load and stiffness. For each variable in b, c and e the mean (solid centre lines), ±1.0 SD (dotted lines) and ±2.0 SD. (grey boxes) for WT mice (n = 320) are shown. Individual data-points for each parameter in Auts2+/-, Cttnbp2−/−, Dact3−/− and Ldlrad4−/− lines are shown as green, pink, blue and orange dots, respectively (n = 6 biologically independent mice per genotype). The mean value for each individual phenotype parameter is indicated by a solid bold line. Mean parameters that lie greater or less than two standard deviations from the WT reference mean are considered outliers and are indicated by an asterisk (*), coloured according to the individual mouse line.

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