MMP-9 is important for stimulation of angiogenesis by osteoclasts in bone explants. (A) PTHrP-induced metatarsal angiogenesis is blunted in Mmp9^−/− explants. Sample (original magnification ×2) images of WT or Mmp9^−/− C57BL/6 metatarsal explants treated with vehicle or 100nM PTHrP as indicated and stained for CD31. Images acquired as in Figure 2. (B) Angiogenic response to PTHrP is significantly less in Mmp9^−/− than in WT metatarsal explants. Metatarsals from 7 WT and 6 Mmp9^−/− litters were treated with 100nM PTHrP or vehicle. The mean fold change from control in CD31⁺ area per litter for all litters ± SEM is reported. *P < .05, difference in treatment response between genotypes. PTHrP significantly stimulated angiogenesis in WT but not in Mmp9^−/− metatarsals, as determined by the ratio t test comparing vehicle and PTHrP-treated means for each litter. (C) PTHrP increases bone resorption in WT but not in Mmp9^−/− metatarsal explants. CTX assayed from conditioned media collected from days 1 to 3 or 4 to 6 of culture of all 7 WT and 6 knockout litters and reported as mean fold change from control. *P < .05, treatment response compared with vehicle. NS indicates not significant.