Bafilomycin A1 in bone resorption and tooth eruption in dogs

Tooth eruption depends on bone resorption to form an eruption pathway. We have previously shown that a 2-wk local infusion of bafilomycin A1, an inhibitor of vacuolar H(+)-ATPases in osteoclasts, into the crypts of erupting mandibular premolars in dogs blocks bone resorption during this period and eruption of these teeth is delayed for 8 wk. Here we report the limits of inhibition of resorption that still permit eruption of these teeth. In 3 dogs 10(-6) M bafilomycin was delivered by osmotic minipumps early (18 wk) in eruption to the fourth premolar for 1, 3 or 4 wk. Radiographs taken at weekly intervals thereafter showed that bafilomycin delivery for 1 wk delayed eruption for 3 wk, delivery for 3 wk delayed eruption 9 wk and delivery for 4 wk prevented eruption. These data show that tooth eruption is delayed in direct proportion to the time resorption is blocked, and that this process for dog premolars cannot be blocked for more than 3 wk with 10(-6) M bafilomycin without blocking eruption itself.