Department of Chemistry, Case Western Reserve University, Cleveland, OH 44106, USA.
Department of Biochemistry and Molecular Biology, Jeonbuk National University Medical School, Jeonju 54896, Republic of Korea.
Int J Mol Sci. 2023 Jun 27;24(13):10714. doi: 10.3390/ijms241310714.
Periodontitis is an inflammatory disease caused by microorganisms that induce the destruction of periodontal tissue. Inflamed and damaged tissue produces various inflammatory cytokines, which activate osteoclasts and induce alveolar bone loss and, eventually, tooth loss. Sirt6 expression suppresses inflammation and bone resorption; however, its role in periodontitis remains unclear. We hypothesized that Sirt6 has a protective role in periodontitis. To understand the role of Sirt6 in periodontitis, we compared periodontitis with ligature placement around the maxillary left second molar in 8-week-old control (C57BL/6J) male mice to Sirt6-overexpressing Tg (Sirt6Tg) mice, and we observed the resulting phenotypes using micro-CT. MDL801, a Sirt6 activator, was used as a therapy for periodontitis through oral gavage. Pro-inflammatory cytokines and increased osteoclast numbers were observed in alveolar bone tissue under periodontitis surgery. In the same condition, interestingly, protein levels from Sirt6 were the most downregulated among sirtuins in alveolar bone tissue. Based on micro-CT and CEJ-ABC distance, Sirt6Tg was observed to resist bone loss against ligature-induced periodontitis. Furthermore, the number of osteoclasts was significantly reduced in Sirt6Tg-ligated mice compared with control-ligated mice, although systemic inflammatory cytokines did not change. Consistent with this observation, we confirmed that bone loss was significantly reduced when MDL801, a Sirt6 activator, was included in the ligation mouse model. Our findings demonstrate that Sirt6 activation prevents bone loss against ligature-induced periodontitis. Thus, a Sirt6 activator may provide a new therapeutic approach for periodontitis.
牙周炎是一种由微生物引起的炎症性疾病，可导致牙周组织破坏。发炎和受损的组织会产生各种炎症细胞因子，这些细胞因子激活破骨细胞，导致牙槽骨丧失，最终导致牙齿脱落。Sirt6 的表达可抑制炎症和骨质吸收；然而，其在牙周炎中的作用尚不清楚。我们假设 Sirt6 在牙周炎中具有保护作用。为了了解 Sirt6 在牙周炎中的作用，我们将牙周炎与上颌左侧第二磨牙周围结扎的雄性 8 周龄对照（C57BL/6J）小鼠进行了比较，将 Sirt6 过表达 Tg（Sirt6Tg）小鼠，并用 micro-CT 观察其表型。用 Sirt6 激活剂 MDL801 通过口服灌胃治疗牙周炎。在牙周炎手术后，观察到牙槽骨组织中促炎细胞因子和破骨细胞数量增加。在相同条件下，有趣的是，Sirt6 蛋白水平在牙槽骨组织中的所有 Sirtuins 中下调最明显。基于 micro-CT 和 CEJ-ABC 距离，观察到 Sirt6Tg 可抵抗结扎引起的牙周炎导致的骨质流失。此外，与对照结扎小鼠相比，Sirt6Tg 结扎小鼠的破骨细胞数量显著减少，尽管系统性炎症细胞因子没有变化。与这一观察结果一致，我们证实，当 Sirt6 激活剂 MDL801 包含在结扎小鼠模型中时，骨质流失显著减少。我们的研究结果表明，Sirt6 激活可防止结扎引起的牙周炎导致的骨质流失。因此，Sirt6 激活剂可能为牙周炎提供一种新的治疗方法。
