Osteoclast polarization and orthodontic tooth movement.
Osteoclast polarization and orthodontic tooth movement.
复制标题
DOI：
10.1111/j.1601-6343.2009.01443.x
复制
发表时间：
2009-05
影响因子：
3.1
通讯作者：
L. Holliday;D. Ostrov;T. Wronski;C. Dolce
中科院分区：
文献类型：
--
作者：
L. Holliday;D. Ostrov;T. Wronski;C. Dolce
破骨细胞在接触到与骨相关的激活信号时会发生凋亡。极化是骨吸收所必需的，涉及高度专业化的机制，代表了破骨细胞特异性治疗药物开发的有吸引力的目标。这种试剂的一个潜在用途是在空间离散位置阻止牙齿移动以提供正畸锚固。材料和方法我们小组的研究是针对开发抑制破骨细胞极化的药物，并正在努力开发实验调节正畸牙齿移动的方法。我们在大鼠模型中使用整合素和基质金属蛋白酶抑制剂进行了“原理验证”实验，证明了正畸牙齿移动的药理学阻断作用。结果我们发现了破骨细胞骨吸收的新机制。空泡H（+）-ATP酶与破骨细胞特有的微丝骨架之间的相互作用被描述和表征。我们的小组现在正在寻求利用这一新的知识，再加上一个新兴的技术，基于超级计算机的分子建模的合理发展的新的，破骨细胞特异性治疗剂。结论对破骨细胞骨吸收的分子机制的新认识为选择性调节破骨细胞活性的药物提供了新的机会。此类药物可能有助于正畸实践的发展。
INTRODUCTION Osteoclasts polarize when they contact activation signals that are associated with bone. Polarization is required for bone resorption and involves highly specialized mechanisms that represent attractive targets for the development of osteoclast-specific therapeutic agents. One potential use of such agents is to block tooth movement in spatially discrete locations to provide orthodontic anchorage. MATERIALS AND METHODS Our group's research was directed toward the development of agents that inhibited the polarization of osteoclasts, and efforts were underway to develop means to experimentally modulate orthodontic tooth movement. We performed 'proof-in-principle' experiments demonstrating pharmacological blockades of orthodontic tooth movement using integrin and matrix metalloproteinase inhibitors in a rat model. RESULTS We identified novel mechanisms underlying osteoclast bone resorption. Interactions between vacuolar H(+)-ATPase and the microfilament cytoskeleton that were unique to osteoclasts were described and characterized. Our group is now seeking to make use of this new knowledge, coupled with an emerging technique, supercomputer-based molecular modeling for the rational development of novel, osteoclast-specific therapeutic agents. CONCLUSION Fresh insight into the molecular details of osteoclastic bone resorption provides new opportunities for identifying agents to selectively modulate osteoclast activity. Such agents may contribute to evolution of the practice of orthodontics.