Fig. 7.

FST overexpression reduces BMD and induces tibia fractures. (A) Representative images of 10-wk-old mice. The boxed region is magnified to display fractured tibia in F66 mice, which is pointed by a red arrow. (B) Representative DXA images of 10-wk-old mice, and microCT images of F66 mouse’s fractured tibia in the boxed region. The cross sectional image at the position indicated by yellow dashed line is shown in the Bottom panel. (C) DXA analysis of 10-wk-old mice (n = 5 for WT mice, n = 5 for Mstn^−/− mice, and n = 8 for F66 mice). (D) Representative microCT images of 10-wk-old mouse tibia. Fractured tibias of F66 mice were excluded from microCT analysis. Tb. bones are colored in orange and Ct. bones (1 mm in height) are colored in yellow. Raw cross sectional images of the colored middle and distal diaphysis are displayed in the Bottom panel. (E) Histomorphometric analysis of Ct. bones of 10-wk-old mice (n = 5 each). (F) Representative microCT images of 10-wk-old mouse distal hindlimbs cross sectioned at the level where tibia and fibula start to fuse. The red dotted lines mark muscle boundaries. C. bones are colored in yellow. (G) Representative microCT images of 10-wk-old mouse vertebrae (L1). Tb. bone of the vertebral body is colored in orange. (H) Histomorphometric analysis of L1 Tb. bone in 10-wk-old mice (n = 5 each). (I) A model for regulation of skeletal muscle and bone mass by FST. FST enhances skeletal muscle mass by inhibiting MSTN, while decreasing BMD by blocking GDF11. All scale bars are displayed with actual size values. All data represent mean ± SEM. *P < 0.05, **P < 0.01, and ***P < 0.001 by ANOVA with Tukey’s post hoc test.