Fig. 1.

Whole-body Sik2/Sik3 ablation increases bone turnover markers and trabecular bone mass. Twelve-week-old control (Sik2^f/f; Sik3^f/f) and mutant (Sik2^f/f; Sik3^f/f; ubiquitin-Cre^ERt2) were treated with tamoxifen (1 mg IP Q48H ×3 doses). (A) Bone turnover markers (alkaline phosphatase (AlkP), P1NP), and CTX) were measured 2, 4, 8, and 16 wk after tamoxifen treatment. Serum analysis of mice after tamoxifen administration showed dramatic increases in turnover markers at each time point (n = 3 to 6 mice per group). (B) Tibia histology by hematoxylin and eosin (HE) stain. (C) Safranin O and (D) sclerostin immunohistochemistry were performed. Sclerostin levels were substantially down-regulated by Sik2/Sik3 gene deletion at each time point. (E) Distal femur micro-CT results showed significantly increased bone volume and mineral density 8 and 16 wk after tamoxifen treatment. Images are shown on the Left, and key trabecular (bone volume per tissue volume (BV/TV) and trabecular BMD) and cortical (cortical thickness) parameters are shown on the Right (n = 6 to 9 mice per group). See also Dataset S1 for full micro-CT data from 8- and 16-wk chase animals. P values versus control are shown in the figure. Two-sided t tests were used (A and E). Data are expressed as mean ± SEM.