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

本研究探讨了降胆固醇药物他汀类药物对成骨细胞的合成代谢作用。结果，他汀类药物的应用以一种剂量依赖的方式增加了细胞数量。此外，他汀类药物还能促进成骨细胞形成骨结节。此外，他汀类药物的应用还增加了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。第二，他汀类药物对人工骨腔的作用作为体内研究。在6周龄大鼠胫骨上建立人工骨腔，腔内注射他汀类药物。结果显示，所有组包括对照组(注射赋形剂)均有新骨形成，但他汀组在早期有显著的新骨形成。他汀组破骨细胞的形成受到明显抑制。聚合酶链式反应研究表明，局部应用他汀类药物增加了成骨细胞的信号转导。相反，破骨细胞信号耗尽。第三，研究了他汀类药物对钛种植体周围骨形成的影响。因此，全身应用他汀类药物可刺激12周龄大鼠胫骨植入钛种植体周围的成骨，即使在骨质疏松的情况下也是如此。综上所述，他汀类药物可促进骨形成并抑制骨吸收。提示他汀类药物用于骨再生治疗的可能性。

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.