Figure 6. Role of aberrant BMP signaling in osteochondromagenesis in Fsp1-Ext1^CKO mice.

(A) BMP signaling is upregulated in the perichondrium of Fsp1-Ext1^CKO mice. Frozen sections of a rib bone from P14 Fsp1-Ext1^CKO and control (Ext1^flox/flox; WT) littermates were double-labeled with anti-pSmad1/5/8 antibody (green) and TO-PRO-3 (blue). Broken lines depict the perichondrium/growth plate boundary. Areas indicated by rectangles are enlarged in neighboring panels. PC, perichondrium; GP, growth plate; M, muscle. Scale bar: 0.1 mm. (B and C) Effects of LDN-193189 treatment on osteochondromagenesis in Fsp1-Ext1^CKO mice. Fsp1-Ext1^CKO mice were treated with LDN-193189 as described in Methods. (B) Representative images of whole-mount skeletal preparations of the rib cage of LDN-193189- and vehicle-treated mice. A preparation of a WT mouse is shown for comparison (WT). Scale bar: 1 mm. (C) Quantitative assessment of the effect of LDN-193189 on the number of osteochondromas in rib bones, the length of the radius, and the body weight. Means ± SD (n = 8) are shown as horizontal bars. **P < 0.01, ***P < 0.001 by Student’s t test.