A novel inhibitor of vacuolar ATPase, FR202126, prevents alveolar bone destruction in experimental periodontitis in rats.
A novel inhibitor of vacuolar ATPase, FR202126, prevents alveolar bone destruction in experimental periodontitis in rats.
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一种新型空泡 ATP 酶抑制剂 FR202126 可预防大鼠实验性牙周炎中的牙槽骨破坏。
DOI：
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发表时间：
2005
影响因子：
2
通讯作者：
N. Chida
中科院分区：
文献类型：
--
作者：
K. Niikura;N. Takeshita;N. Chida
破骨细胞质膜上表达的空泡ATP酶（V-ATP酶）所形成的酸性微环境被认为是骨吸收所必需的。本研究探讨了一种新的V-ATP酶抑制剂，FR 202126，在减少大鼠实验性牙周炎引起的牙槽骨丢失的疗效。FR 202126抑制小鼠破骨细胞质膜囊泡的H+转运，而对线粒体ATP酶和胃H+，K+-ATP酶的H+转运无影响，表明FR 202126是V-ATP酶的特异性抑制剂。正如从机理上所预期的，FR 202126显著抑制体外骨吸收，无论加入什么样的骨吸收因子。此外，FR 202126还能够对体内骨吸收发挥抑制作用。实验性牙周炎是通过结扎线绑在第一和第二上颌磨牙之间的接触。结扎线插入7天，通过激活破骨细胞引起牙槽骨破坏。FR 202126（u.i.d.）经口给药显著阻止实验性牙周炎牙槽骨丢失，为牙周病的治疗提供了新的途径。
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.
影响因子：
6.7
作者：
REINHARDT, RA;MASADA, MP;ALLISON, AC
通讯作者：
ALLISON, AC
影响因子：
56.9
作者：
BLAIR, HC;TEITELBAUM, SL;GLUCK, S
通讯作者：
GLUCK, S
DOI：
10.1073/pnas.85.21.7972
发表时间：
1988-11-01
影响因子：
11.1
作者：
BOWMAN, EJ;SIEBERS, A;ALTENDORF, K
通讯作者：
ALTENDORF, K