Department of Orthodontics, Tokyo Dental College, Tokyo, Japan.
Sci Rep. 2022 Jun 2;12(1):9243. doi: 10.1038/s41598-022-13217-x.
Semaphorin 3A (Sema3A) promotes osteoblast differentiation and inhibits osteoclast differentiation. In the present study, we observed the regulation of alveolar bone remodeling by Sema3A during orthodontic tooth movement (OTM). Four inflammatory cytokines (IL-1β, IL-6, TNFα, and INF-γ) involved in OTM were applied to osteoblasts in vitro, and Sema3A expression was determined by reverse-transcription quantitative polymerase chain reaction (RT-qPCR). In vivo, springs were attached to the maxillary first molars of C56BL/6J mice (OTM model) and the localization of Sema3A was confirmed by immunofluorescent. Recombinant Sema3A (rSema3A) was locally injected into the OTM model. Inflammatory cytokine localization in the OTM model was confirmed by immunohistochemistry. In vivo, more Sema3A was observed on the tension side in the OTM group. Injection of rSema3A into the OTM model increased mineralization on the tension side and decreased the number of osteoclasts on the compression side. In vitro, IL-1β significantly increased Sema3A mRNA levels. Immunohistochemistry for IL-1β in vivo showed more concentrated staining in the periodontal ligament on the tension side than on the compression side. In summary, our findings revealed the distribution of Sema3A in the periodontal ligament and demonstrated that rSema3A administration promotes bone formation and inhibits bone resorption during OTM.
信号素 3A（Sema3A）促进成骨细胞分化并抑制破骨细胞分化。本研究观察了 Sema3A 在正畸牙齿移动（OTM）过程中对牙槽骨重塑的调节作用。体外将四种参与 OTM 的炎症细胞因子（IL-1β、IL-6、TNFα 和 INF-γ）应用于成骨细胞，并通过逆转录定量聚合酶链反应（RT-qPCR）测定 Sema3A 的表达。体内，将弹簧附着在 C56BL/6J 小鼠的上颌第一磨牙上（OTM 模型），并用免疫荧光法确认 Sema3A 的定位。将重组 Sema3A（rSema3A）局部注射到 OTM 模型中。通过免疫组织化学证实 OTM 模型中炎症细胞因子的定位。体内，在 OTM 组中观察到张力侧有更多的 Sema3A。向 OTM 模型中注射 rSema3A 增加了张力侧的矿化，减少了压缩侧的破骨细胞数量。体外，IL-1β 显著增加了 Sema3A 的 mRNA 水平。体内的 IL-1β 免疫组织化学显示，张力侧牙周韧带的染色比压缩侧更集中。综上所述，我们的研究结果揭示了 Sema3A 在牙周韧带中的分布，并表明 rSema3A 给药在 OTM 过程中促进骨形成并抑制骨吸收。
