Single Local Injection of Epigallocatechin Gallate-Modified Gelatin Attenuates Bone Resorption and Orthodontic Tooth Movement in Mice
Single Local Injection of Epigallocatechin Gallate-Modified Gelatin Attenuates Bone Resorption and Orthodontic Tooth Movement in Mice
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DOI：
10.3390/polym10121384
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发表时间：
2018-12-01
期刊：
影响因子：
5
通讯作者：
Nakamura, Yoshiki
中科院分区：
文献类型：
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作者：
Katsumata, Yuta;Kanzaki, Hiroyuki;Nakamura, Yoshiki
破骨细胞骨吸收使正畸治疗中的正畸牙齿移动（OTM）成为可能。此前，我们证明局部注射表没食子儿茶素没食子酸酯（EGCG）成功减缓了OTM的发生率；然而，需要重复注射。在本研究中，我们生产了液体形式的 EGCG 修饰明胶 (EGCG-GL)，并检查了 EGCG-GL 在延长 EGCG 释放、NF-E2 相关因子 2 (Nrf2) 激活、破骨细胞生成抑制、骨破坏和 OTM 方面的特性。我们发现，在小鼠巨噬细胞系 RAW264.7 中，EGCG-GL 既能延长 EGCG 的释放，又能诱导抗氧化酶基因的表达，例如血红素加氧酶 1 (Hmox1) 和谷氨酸半胱氨酸连接酶 (Gclc)。 EGCG-GL 减弱细胞内活性氧 (ROS) 水平，由核因子 kB 配体受体激活剂 (RANKL) 诱导，并在体外抑制 RANKL 介导的破骨细胞生成。通过向雄性 BALB/c 小鼠的颅盖重复注射脂多糖 (LPS) 诱导的骨破坏动物模型表明，在第 1 天单次注射 EGCG-GL 可以成功抑制 LPS 介导的骨破坏。此外，雄性小鼠上颌第一磨牙的实验性 OTM 通过第一天单次 EGCG-GL 注射而减弱。总之，EGCG-GL 通过增加抗氧化酶的表达来减弱细胞内 ROS 信号传导，从而延长 EGCG 的释放并抑制破骨细胞生成。这些结果表明 EGCG-GL 对于破坏性骨疾病和控制牙槽骨代谢都是一种有益的治疗方法。
Osteoclastic bone resorption enables orthodontic tooth movement (OTM) in orthodontic treatment. Previously, we demonstrated that local epigallocatechin gallate (EGCG) injection successfully slowed the rate of OTM; however, repeat injections were required. In the present study, we produced a liquid form of EGCG-modified gelatin (EGCG-GL) and examined the properties of EGCG-GL with respect to prolonging EGCG release, NF-E2-related factor 2 (Nrf2) activation, osteoclastogenesis inhibition, bone destruction, and OTM. We found EGCG-GL both prolonged the release of EGCG and induced the expression of antioxidant enzyme genes, such as heme oxygenase 1 (Hmox1) and glutamate-cysteine ligase (Gclc), in the mouse macrophage cell line, RAW264.7. EGCG-GL attenuated intracellular reactive oxygen species (ROS) levels were induced by the receptor activator of nuclear factor-kB ligand (RANKL) and inhibited RANKL-mediated osteoclastogenesis in vitro. An animal model of bone destruction, induced by repeat Lipopolysaccharide (LPS)-injections into the calvaria of male BALB/c mice, revealed that a single injection of EGCG-GL on day-1 could successfully inhibit LPS-mediated bone destruction. Additionally, experimental OTM of maxillary first molars in male mice was attenuated by a single EGCG-GL injection on day-1. In conclusion, EGCG-GL prolongs the release of EGCG and inhibits osteoclastogenesis via the attenuation of intracellular ROS signaling through the increased expression of antioxidant enzymes. These results indicate EGCG-GL would be a beneficial therapeutic approach both in destructive bone disease and in controlling alveolar bone metabolism.