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的合成代谢作用。首先，研究了他汀类药物对体外培养的成骨细胞的影响。结果，他汀类药物的应用以剂量依赖性方式增加了细胞数量。此外，成骨细胞的骨结节的形成被他汀刺激。此外，他汀类药物的应用还增加了骨形成所必需的信号蛋白smad-2和4的表达。第二，体内研究了他汀类药物对人工骨腔的影响。在6周龄大鼠胫骨建立人工骨腔，腔内注射他汀。结果，包括对照（载体注射）在内的所有组均显示新骨形成，然而，他汀组在早期阶段显示出显著量的新骨形成。此外，他汀组破骨细胞的形成明显受到抑制。PCR研究显示局部应用他汀类药物可增加成骨细胞的信号转导。相反，骨细胞信号被耗尽。第三，研究了他汀类药物对钛种植体周围成骨的影响。结果表明，全身给予他汀类药物可刺激植入12周龄大鼠胫骨的钛种植体周围的骨生成，即使在骨质疏松的情况下也是如此，总之，他汀类药物的给药可增加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.