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首页> 外文期刊>The Journal of toxicological sciences >A novel inhibitor of vacuolar ATPase, FR202126, prevents alveolar bone destruction in experimental periodontitis in rats.
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A novel inhibitor of vacuolar ATPase, FR202126, prevents alveolar bone destruction in experimental periodontitis in rats.

机译：一种新型的液泡ATPase抑制剂FR202126可防止大鼠实验性牙周炎中牙槽骨的破坏。

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摘要

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.
机译：破骨细胞质膜中表达的液泡ATPase（V-ATPase）形成的酸性微环境被认为对于骨吸收是必不可少的。这项研究检查了新型V-ATPase抑制剂FR202126在减少大鼠实验性牙周炎引起的牙槽骨丢失方面的功效。 FR202126抑制了鼠破骨细胞质膜囊泡中的H +转运，而FR202126对线粒体ATPase或胃H +，K + -ATPase的H +转运没有影响，表明FR202126是V-ATPase的特异性抑制剂。如从该机理所预期的那样，无论添加了什么骨吸收因子，FR202126都显着抑制了体外骨吸收。而且，FR202126还能够对体内骨吸收产生抑制作用。实验性牙周炎是由绑扎在第一和第二上颌磨牙之间的接触周围的结扎线引起的。插入结扎线7天通过激活破骨细胞引起肺泡骨破坏。口服FR202126（u.i.d.）可显着预防实验性牙周炎中牙槽骨的丢失，这可能为治疗牙周疾病提供了一种新方法。

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