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A Basic Research for Bone Induction at Maxillofacial Region Using Cholesterol-Lowering Drug

降胆固醇药物颌面骨诱导的基础研究

基本信息

批准号：
14370638
负责人：
KOYANO Kiyoshi
金额：
$ 8.51万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370638/
关键词：
statin bone regeneration calcified tissue osteoclasts osteoblasts チタン smad 骨

项目摘要

In the present study, anabolic effect of cholesterol-lowering drug, statin, was investigated.First, effect of statin on the cultured osteoblastic cells was studied. As a result, the application of statin increased the number of cells in a dose-dependent manner. Furthermore, the formation of bone nodule by the osteoblastic cells was stimulated by statin. The application of statin, in addition, was also increased the expression of smad-2 and 4, both of which were signal proteins essential for bone formation.Second, the effect of statin for artificial bone cavity was performed as an in vivo study. Artificial bone cavity was created in the tibia of 6-week-old rat and statin was injected into the cavity. As a result, all groups including control (vehicle injection) showed the formation of new bone, however, statin group showed the statistically-significant amount of new bone formation in the early stage. In addition, the formation of osteoclast in statin group was significantly inhibited. The PCR study showed that the local administration of statin increased the signaling of osteoblast. On the contrary, osteoclastic signal was depleted. These results suggested the anabolic effect of the statin for bone healingThird, the effect of statin for osteogenesis around the titanium implant was studied. As a result, systemic administration of statin stimulated the osteogenesis around the titanium implants inserted into the 12-weeks-old rat tibiae, even in the osteoporotic situation.In summary, it was suggested that the administration of statin increased the bone formation and inhibited the bone resorption. The possibility of statin for the bone regenerative therapy was indicated.

在本研究中，研究了降胆固醇药物他汀的合成代谢作用。首先，研究了他汀类药物对体外培养成骨细胞的影响。结果，他汀类药物的应用以剂量依赖的方式增加了细胞数量。此外，他汀类药物可促进成骨细胞形成骨结节。此外，他汀类药物的应用也增加了smad-2和4的表达，这两种蛋白都是骨形成所必需的信号蛋白。其次，他汀类药物对人工骨腔的作用进行了体内研究。在6周龄大鼠胫骨内建立人工骨腔，并注入他汀类药物。结果，包括对照组（载体注射）在内的所有组均出现新骨形成，而他汀类药物组早期新骨形成量有统计学意义。此外，他汀类药物组破骨细胞的形成明显受到抑制。PCR研究表明，局部给药他汀类药物可增加成骨细胞的信号转导。相反，破骨细胞信号减弱。这些结果提示他汀类药物对骨愈合的合成代谢作用。第三，研究他汀类药物对钛种植体周围成骨的影响。结果，即使在骨质疏松的情况下，系统给药他汀类药物也能刺激12周龄大鼠胫骨钛植入物周围的成骨。综上所述，他汀类药物可促进骨形成，抑制骨吸收。提示他汀类药物用于骨再生治疗的可能性。