Department of Periodontology and Endodontology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Oral Management Center, Nagasaki University Hospital, Nagasaki, Japan.
J Periodontal Res. 2021 Jan;56(1):186-194. doi: 10.1111/jre.12813. Epub 2020 Nov 27.
Traumatic occlusion can cause bone resorption without bacterial infection. Although bone resorption in periodontitis has been relatively well studied, little is known about bone resorption by traumatic occlusion. High-mobility group box 1 (HMGB1) is released from damaged tissue and has been recently shown to promote bone resorption in a murine periodontitis model and may also promote bone resorption by traumatic occlusion. The present study aimed to examine whether HMGB1 accelerates bone resorption by traumatic occlusion in mice.
Occlusal trauma was induced in the lower left first molar of mice by bonding a wire to the upper left first molar, and bone resorption and osteoclast formation were evaluated histochemically. The expression of HMGB1, Toll-like receptor 4 (TLR4; the receptor for HMGB1), and receptor activator of NFκB ligand (RANKL; an essential osteoclast differentiation factor) was evaluated immunohistologically. In addition, mice were administrated with an anti-HMGB1-neutralizing antibody to analyze the role of HMGB1.
Bone resorption and osteoclast formation gradually increased until day 5 at the furcation area after the application of traumatic occlusion. Expression of HMGB1 was observed at the furcation area on day 1, but was attenuated by day 3. Expression of RANKL gradually increased until day 3, but was attenuated by day 5. Administration of anti-HMGB1 antibody significantly reduced the number of osteoclasts and the expression of RANKL and TLR4 at the furcation area.
Release of HMGB1 in the root furcation area accelerated bone resorption by up-regulating RANKL and TLR4 expression in mice with traumatic occlusion.
创伤性咬合可在无细菌感染的情况下引起骨质吸收。虽然牙周炎的骨质吸收已得到了较为充分的研究，但对于创伤性咬合引起的骨质吸收知之甚少。高迁移率族蛋白 B1（HMGB1）从受损组织中释放出来，最近有研究表明其可促进牙周炎小鼠的骨质吸收，也可能促进创伤性咬合引起的骨质吸收。本研究旨在观察 HMGB1 是否会加速小鼠创伤性咬合引起的骨质吸收。
通过在上颌第一磨牙上绑定金属丝，使小鼠左下第一磨牙产生咬合创伤，通过组织化学方法评估骨质吸收和破骨细胞形成。通过免疫组织化学方法评估 HMGB1、Toll 样受体 4（HMGB1 的受体）和核因子-κB 受体激活剂配体（RANKL；一种必不可少的破骨细胞分化因子）的表达。此外，通过给予抗 HMGB1 中和抗体来分析 HMGB1 的作用。
创伤性咬合应用后第 5 天，在分叉区逐渐出现骨质吸收和破骨细胞形成。第 1 天在分叉区观察到 HMGB1 的表达，但第 3 天减弱。RANKL 的表达逐渐增加，直到第 3 天，但在第 5 天减弱。在分叉区给予抗 HMGB1 抗体可显著减少破骨细胞数量和 RANKL、TLR4 的表达。
HMGB1 在根分叉区的释放通过上调 RANKL 和 TLR4 的表达，加速了创伤性咬合小鼠的骨质吸收。
