Figure 3.

Systemic treatment of NELL-PEG increases bone formation and bone turnover rate. A: Representative images of dynamic bone labeling of Calcein (week 1) and Alizarin Red Complexon (week 3) at the fracture site. The phosphate-buffered saline (PBS) group shows nonunion callus with less Alizarin label deposited at the fracture site, whereas the NELL-PEG group shows a high intensity of bone labels deposited within the callus. Dashed lines represent the cortical border of radius. Boxed areas in the top row represent midcallus areas, which are shown at higher-power magnification in bottom row. B and C: Quantification of bone labeling histomorphometric analysis reveals significant increases of mineral apposition rate (MAR) and bone formation rate (BFR). D: Representative images of bone turnover rate assessment by the microPET-CT scan after injection of the ¹⁸F-NaF ion. The NELL-PEG group shows increased uptake of the tracer at the fracture site compared with the PBS group. E: Quantification of the mean value ratio at the fracture site exhibits significantly higher tracer uptake in the NELL-PEG group compared with the PBS group. Data are expressed as means ± SD (B, C, and E). ^∗P < 0.05. Scale bars: 8 mm (A, top row, and D); 16 mm (A, bottom row). Original magnification: ×2 ( A, top row); ×20 (A, bottom row). BS, bone surface; ID, injected dose.