Bis-enoxacin Inhibits Bone Resorption and Orthodontic Tooth Movement
| Autor: | E J, Toro, J, Zuo, A, Gutierrez, A, Guiterrez, R L, La Rosa, A J, Gawron, V, Bradaschia-Correa, V, Arana-Chavez, C, Dolce, M F, Rivera, L, Kesavalu, I, Bhattacharyya, J K, Neubert, L S, Holliday |
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| Rok vydání: | 2013 |
| Předmět: |
Enoxacin
Male Vacuolar Proton-Translocating ATPases medicine.medical_specialty Tooth Movement Techniques Alveolar Bone Loss Osteoclasts Apoptosis Bone resorption Rats Sprague-Dawley Osteoclast In vivo Internal medicine medicine Animals General Dentistry Cells Cultured Nucleic Acid Synthesis Inhibitors Diphosphonates biology Caspase 3 Acid phosphatase Research Reports Actin cytoskeleton Molecular biology Rats Actin Cytoskeleton Endocrinology medicine.anatomical_structure RANKL biology.protein Cattle Fetal bovine serum Protein Binding medicine.drug |
| Zdroj: | Journal of Dental Research. 92:925-931 |
| ISSN: | 1544-0591 0022-0345 |
| DOI: | 10.1177/0022034513501876 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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