Suzuki Noriyuki, Takimoto Koyo, Kawashima Nobuyuki
Department of Pulp Biology and Endodontics, Division of Oral Health Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Department of Pulp Biology and Endodontics, Division of Oral Health Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
J Endod. 2015 Sep;41(9):1474-9. doi: 10.1016/j.joen.2015.04.013. Epub 2015 May 16.
Cathepsin K is highly expressed in osteoclasts and plays an essential role in bone resorption. NC-2300 is an artificially designed cathepsin K inhibitor, and its application to experimentally induced arthritis induces down-regulation of bone destruction. In this study, we evaluated the effects of NC-2300 on inflammation and bone destruction in experimentally induced rat periapical lesions.
The dental pulps of lower first molars in rats were extirpated, and the pulp chambers were left open to the oral environment. NC-2300 and phosphate-buffered saline were administered orally twice a day in the experimental and control groups, respectively. Animals were sacrificed on day 21, and the mandibles were extracted. The left hemimandibles were used for micro-computed tomographic and histologic examination. For the right hemimandibles, RNA was extracted from the periapical tissues surrounding the root apices, and inflammatory mediator expression was examined by real-time polymerase chain reaction using complementary DNA converted from extracted RNA.
The size of the periapical lesion, number of tartrate-resistant acid phosphatase-positive osteoclasts and major histocompatibility complex class II molecule-expressing macrophages in the experimental group decreased significantly when compared with the control group. The expression of proinflammatory cytokines in the experimental group was significantly suppressed when compared with the control group.
These results suggest that the cathepsin K inhibitor may inhibit not only cathepsin K activity in osteoclasts but also inflammatory mediator synthesis relating to osteoclastogenesis, and these synergistic effects may be involved in the suppression of periapical lesion expansion.
组织蛋白酶K在破骨细胞中高表达，在骨吸收中起重要作用。NC - 2300是一种人工设计的组织蛋白酶K抑制剂，将其应用于实验性诱导的关节炎可导致骨破坏下调。在本研究中，我们评估了NC - 2300对实验性诱导的大鼠根尖周病变中炎症和骨破坏的影响。
摘除大鼠下颌第一磨牙的牙髓，使髓腔向口腔环境开放。分别在实验组和对照组中，每天口服两次NC - 2300和磷酸盐缓冲盐水。在第21天处死动物并取出下颌骨。左侧半下颌骨用于显微计算机断层扫描和组织学检查。对于右侧半下颌骨，从根尖周围的根尖周组织中提取RNA，并使用从提取的RNA转化而来的互补DNA通过实时聚合酶链反应检测炎症介质表达。
与对照组相比，实验组根尖周病变的大小、抗酒石酸酸性磷酸酶阳性破骨细胞的数量以及表达主要组织相容性复合体II类分子的巨噬细胞数量均显著减少。与对照组相比，实验组促炎细胞因子的表达受到显著抑制。
这些结果表明，组织蛋白酶K抑制剂不仅可能抑制破骨细胞中的组织蛋白酶K活性，还可能抑制与破骨细胞生成相关的炎症介质合成，并且这些协同作用可能参与抑制根尖周病变的扩展。
