Figure 9. β-Catenin stabilization enables synovial sarcomagenesis from preosteoblasts.

(A) Kaplan-Meier plot of tumorigenesis among OsxCre^ERT mice bearing hSS2, Ctnnb1^ex3fl, or both and that received tamoxifen at 2 weeks of age (solid line; n = 7; log rank test vs. control Z score = 3.15 and P =0.0016) or 4 weeks of age (dotted line; n = 7; Z score = 3.85 and P < 0.001). (B and C) Posteroanterior radiographs of OsxCre^ERT Ctnnb1^ex3fl mice at 12 months of age, showing increased skeletal density, especially in apparently residual primary spongiosal regions, now in the metadiaphysis (open arrowhead). (D and E) OsxCre^ERT hSS2 Ctnnb1^ex3fl mice at age 12 weeks of age with the same findings (open arrowhead) plus periosteal reactive bone and soft-tissue shadows (solid black arrowheads). (F) Gross dissection and (G) GFP fluorescence images show multiple periscapular tumors (solid black arrowheads) in a 12-week-old OsxCre^ERT hSS2 Ctnnb1^ex3fl mouse. (H) Scapular H&E photomicrographs from a control mouse and (I) a OsxCre^ERT hSS2 Ctnnb1^ex3fl mouse, the latter showing tumors (solid black arrowheads). (J) Photomicrographs of H&E staining of femur sagittal sections from a control mouse and (K) a OsxCre^ERT Ctnnb1^ex3fl mouse, the latter showing dense, unremodeled primary spongiosa (open arrowhead). (L) Graph of fractions of trabecular bone area in metaphyseal femora from 12-week-old OsxCre^ERT Ctnnb1^ex3fl/WT or Ctnnb1^WT/WT mice (bars depict the mean; n = 7 femora; P < 0.0001, by 2-tailed Student’s t test). (M) Graph of TRAP⁺ osteoclasts (OCs) per high-power field (HPF) (bars depict the mean; n = 4 femora per group and ≥5 areas counted per femur; P < 0.0001, by 2-tailed Student’s t test). Scale bars: 100 um.