Figure 1: Identification of the miR-23a cluster in bone and in vivo function.

(a) Twenty most highly expressed primary miRNAs in postnatal day 3 (P3) calvarial tissue in fragments per kilobase of transcript per million (FPKM). (b) μCT images of lumbar spines of the osteoblast-specific GOF mouse model overexpressing the cluster under the control of the Collagen type I, alpha 1 (Col1a1) 2.3 kb promoter (Col1a1-miR-23aC; 23aC) and WT mice (3-month-old females). White bars indicate scale of 200 μm. (c) μCT analysis of trabecular bone volume/total bone volume (BV/TV), trabecular bone thickness (Tb.Th), trabecular bone number (Tb.N) and trabecular bone separation (Tb.Sp) in spines of Col1a1-miR-23aC (23aC) and WT mice. Col1a1-miR-23aC mice showed a low bone mass phenotype (3-month-old female; N=7 for WT, N=8 for 23aC). (d) μCT analysis of trabecular BV/TV, Tb.Th, Tb.N and Tb.Sp of spines of 3-month-old males also showed a low bone mass phenotype in GOF mice (N=8 for WT, N=5 for 23aC). (e) μCT analysis of BV/TV in spines of LOF mouse models and WT littermates. Col1a1-miR-23 decoy (23D) and Col1a1-miR-27 decoy (27D) mice showed a low bone mass phenotype, but not Col1a1-miR-24 decoy (24D) mice. Col1a1-miR-23 decoy (N=7 for WT, 11 for 23D); Col1a1-miR-27 decoy (N=8 for WT, 11 for 27D); 24D, Col1a1-miR-24 decoy (N=10 for WT, 7 for 24D). t-test was performed for the statistical analyses. Error bars represent the s.d. *P<0.05, **P<0.01, ***P<0.005 and ****P<0.001.