Bis-enoxacin inhibits bone resorption and orthodontic tooth movement

Enoxacin inhibits binding between the b-subunit of vacuolar h+-atpase (v-atpase) and microfilaments,and also between osteoclast formation and bone resorption in vitro. we hypothesized that a bisphosphonate derivative of enoxacin,bis-enoxacin (be),which was previously studied as a bone-directed antibiotic,might have similar activities. be shared a number of characteristics with enoxacin: it blocked binding between the recombinant b-subunit and microfilaments and inhibited osteoclastogenesis in cell culture with ic50s of about 10 μm in each case. be did not alter the relative expression levels of various osteoclast-specific proteins. even though tartrate-resistant acid phosphatase 5b was expressed,proteolytic activation of the latent pro-enzyme was inhibited. however,unlike enoxacin,be stimulated caspase-3 activity. be bound to bone slices and inhibited bone resorption by osteoclasts on be-coated bone slices in cell culture. be reduced the amount of orthodontic tooth movement achieved in rats after 28 days. analysis of these data suggests that be is a novel anti-resorptive molecule that is active both in vitro and in vivo and may have clinical uses. abbreviations: be,bis-enoxacin; v-atpase,vacuolar h+-atpase; trap,tartrate-resistant acid phosphatase; αmem d10,minimal essential media,alpha modification with 10% fetal bovine serum; sds-page,sodium dodecyl sulfate-polyacrylamide gel electrophoresis; rankl,receptor activator of nuclear factor kappa b-ligand; nfatc1,nuclear factor of activated t-cells; adam,a disintegrin and metalloprotease domain; otm,orthodontic tooth movement. © international & american associations for dental research.