A NOVEL INHIBITOR OF VACUOLAR ATPase, FR202126, PREVENTS ALVEOLAR BONE DESTRUCTION IN EXPERIMENTAL PERIODONTITIS IN RATS
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- NIIKURA Kazuaki
- Pharmacology Research Laboratories, Astellas Pharma Inc.
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- TAKESHITA Nobuaki
- Pharmacology Research Laboratories, Astellas Pharma Inc.
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- CHIDA Noboru
- Pharmacology Research Laboratories, Astellas Pharma Inc.
書誌事項
- タイトル別名
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- novel inhibitor of vacuolar ATPase FR202126 prevents alveolar bone destruction in experimental periodontitis in rats
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説明
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.<br>
収録刊行物
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- The Journal of Toxicological Sciences
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The Journal of Toxicological Sciences 30 (4), 297-304, 2005
一般社団法人 日本毒性学会
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詳細情報 詳細情報について
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- CRID
- 1390001204902566912
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- NII論文ID
- 110002978307
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- NII書誌ID
- AN00002808
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- COI
- 1:CAS:528:DC%2BD28XitVSjtLw%3D
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- ISSN
- 18803989
- 03881350
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- NDL書誌ID
- 7787276
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
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- 抄録ライセンスフラグ
- 使用不可