Pharmacologic targeting of a stem/progenitor population in vivo is associated with enhanced bone regeneration in mice
J. Clin. Invest. Siddhartha Mukherjee, et al. 118:491 doi:10.1172/JCI33102 [Go to this article.]

Figure 1
Bzb treatment increases osteoblasts in vivo. (A) Mice treated with Bzb (0.3 mg/kg i.p.; 3 times/week) showed an increase in the levels of serum osteocalcin over 3 weeks compared with control-treated (saline-treated) mice. In contrast, serum osteocalcin decreased over time in control mice. P = 0.01 by Student’s t test; n = 5 mice each. (B) Micro-CT analysis revealed an increase in trabecular bone volume in drug-treated mice. A representative reconstruction of trabecular bone is shown as 3D reconstruction (left panel, mock treated; right panel, Bzb treated) and as cross sections (left panel, control; right panel, Bzb treated). Scale bar: 1.0 mm. (C) Colony formation from Bzb-treated versus saline-treated (mock-treated) animals showed increased CFU-F, increased Ops (CFU-Alk), and decreased adipocytic colonies (CFU-Adipo). *P = 0.007, n = 8 wells for CFU-F; ^†P < 0.01, n = 9 wells for CFU-Alk; ^‡P = 0.01, n = 12 wells for CFU-Adipo. (D) Histomorphometric analysis of Bzb-treated animals showed increased trabecular connectivity, trabecular volume occupied by bone, and trabecular number. ^ΧP = 0.05, trabecular connectivity; ^ζP = 0.02, trabecular bone volume; ^#P = 0.03, trabecular number/mm. n = 4 femurs. (E) Histological sections of treated animals showed increased bone with normal architecture in trabeculae (H&E-stained samples) but with increased bone volume. Original magnification, ×40. (F) Increased osteoblast number per BSpm in distal femur was observed in Bzb-treated animals. **P = 0.02; n = 3. (G) Increase in mineralization rate in animals treated with Bzb. ^††P < 0.01; n = 6. (H) No significant change was observed in TRAP-stained osteoclasts, quantified by osteoclasts/μm of BSpm. P = 0.53 by Student’s t test.