DRUG REGULATIONS OF BONE RESORPTION IN ALVEOLAR BONE AND ITS MECHANISM OF ACTION

本研究旨在探讨药物对牙槽骨骨吸收的调节作用及其作用机制。应用原位杂交技术研究了低钙饮食大鼠骨基质蛋白基因表达的变化。原位杂交结果显示，低钙饮食组大鼠成骨细胞中胶原、骨桥蛋白、骨钙素和骨唾液酸蛋白的表达均高于对照组。这一观察结果表明，在低钙状态下骨形成活性升高。水杨酸钠，一种非甾体类抗炎药，在小鼠骨髓培养中抑制破骨细胞样细胞的分化和募集。这表明其对骨吸收的抑制作用的机制。从小鼠骨髓中分离的破骨细胞用高尔基体、ER和溶酶体的荧光染料染色，并在共聚焦激光扫描显微镜下随时间观察。在活的破骨细胞中记录胞质细胞器的变化。本研究结果表明，药物对牙槽骨骨吸收的调节作用及其作用机制。这些研究方法为将来开发预防牙槽骨吸收的新药提供了可能。

The following research was performed in order to study the drug regulation of bone resorption occurred in alveolar bone and its mechanism of action. Gene expressions of bone matrix proteins in rats fed with a low calcium diet was studied using a in situ hybridization. In situ hybridization showed the high levels of collagen, osteopontin, osteocalcin and bone sialprotein was located in the osteoblast in rats fed with a low calcium diet compared with the control rats. This observation indicated that bone formation activity was elevated during the low calcium state. Sodium salicylate, a non-steroidal antiinflammatory drug, inhibited the differentiation and the recruitment of osteoclast-like cells in mouse bone marrow culture. This indicates a mechanism of its inhibitory action on bone resorption. Osteoclasts isolated from mouse bone marrow were stained with a fluorescent dyes for Golgi apparatus, ER,and lysosome and were observed with time under the confocal laser scanning microscopy. The changes in cytoplasmic organella were recorded in the living osteoclasts. The present results demonstrates the drug regulations of bone resorption occurred in alveolar bone and its mechanism of action. These research approaches could develop new drugs for preventing alveolar bone resorption in future.