FIGURE 9.

Effects of isoform-selective PI3K inhibitors on osteoclastic resorption. Rabbit osteoclasts were plated on elephant ivory slices and incubated for 48 h in HCO₃⁻-buffered M199 with specified inhibitors. Samples were treated with vehicle (DMSO), wortmannin (1 μm), GS-9820 (1 μm), TGX221 (1 μm), PIK75 (100 nm), or AS252424 (1 μm). A, scanning electron micrographs show representative fields from control (at left) and from sample treated with GS-9820 (at right), illustrating marked reduction in resorptive activity on blockade of PI3K. B and C, ivory was stained with toluidine blue, after which the number of pits and resorbed area were measured. The inhibitors wortmannin, GS-9820, and TGX221 caused a significant decrease of resorbed area (panel B) as well as pit density (panel C). Data are mean ± S.E., n = 3, independent experiments. Results were analyzed by one-way repeated measures ANOVA followed by a Bonferroni's multiple comparisons test. D, resorption pits were significantly more shallow following treatment with GS-9820 and TGX221. Data are maximum pit depths, mean ± S.E., 10 or more pits measured for each condition. * indicates p < 0.05 compared with vehicle.