A novel inhibitor of vacuolar ATPase, FR202126, prevents alveolar bone destruction in experimental periodontitis in rats.

Abstract	An acidic microenvironment formed by vacuolar ATPase (V-ATPase) expressed in plasma membranes of osteoclasts is thought to be indispensable for bone resorption. This study examined the efficacy of a novel V-ATPase inhibitor, FR202126, in reducing alveolar bone loss caused by experimental periodontitis in rats. FR202126 inhibited H+ transport in plasma membrane vesicles of murine osteoclasts, whereas FR202126 exerted no effect on H+ transport of mitochondrial ATPase or gastric H+,K+-ATPase, indicating that FR202126 is a specific inhibitor of V-ATPase. As expected from the mechanism, FR202126 remarkably inhibited in vitro bone resorption whatever bone resorptive factors were added. Moreover, FR202126 was also able to exert an inhibitory effect on in vivo bone resorption. Experimental periodontitis was induced by ligature wire tied around the contact between the first and second maxillary molars. Insertion of ligature wire for 7 days induced alveolar bone destruction by activating osteoclasts. Oral administration of FR202126 (u.i.d.) significantly prevented alveolar bone loss in experimental periodontitis which may offer a new approach to treatment of periodontal disease.
Authors	Kazuaki Niikura, Nobuaki Takeshita, Noboru Chida
Journal	The Journal of toxicological sciences (J Toxicol Sci) Vol. 30 Issue 4 Pg. 297-304 (Dec 2005) ISSN: 0388-1350 [Print] Japan
PMID	16404138 (Publication Type: Journal Article)
Chemical References	2,6-dichloro-N-(3-methyl-4-(3-methyl-2-oxo-1-imidazolidinyl)-8-quinolinyl)benzamide Aminoquinolines Benzamides Vacuolar Proton-Translocating ATPases
Topics	Alveolar Bone Loss (pathology, prevention & control) Aminoquinolines (pharmacology, therapeutic use) Animals Benzamides (pharmacology, therapeutic use) Bone Resorption (prevention & control) Cells, Cultured Disease Models, Animal Dose-Response Relationship, Drug Female Ligation Male Maxillary Diseases (pathology, prevention & control) Mice Molar Osteoclasts (drug effects, enzymology) Periodontitis (drug therapy, etiology, pathology) Rats Rats, Wistar Sex Factors Time Factors Vacuolar Proton-Translocating ATPases (antagonists & inhibitors, metabolism)

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