Yan Boxi, Wang Linchuan, Li Jing, Yang Ruili, Liu Yan, Yu Tingting, He Danqing, Zhou Yanheng, Liu Dawei
Department of Orthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology Beijing, PR China.
Second Clinical Division, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology Beijing, PR China.
Am J Transl Res. 2020 May 15;12(5):1976-1984. eCollection 2020.
This study aims to investigate the effects of leptin, which is a multifunctional hormone, on orthodontic tooth movement (OTM) and the underlying mechanism. Sprague-Dawley rat OTM models were established and divided into two groups with the administration of vehicle or leptin respectively. Stereomicroscope and microcomputed tomography were used to evaluate the amount of OTM. TRAP staining, immunohistochemical and immunofluorescence staining were used to detect osteoclasts and relative protein expressions. After treated with compression force, human periodontal ligament cells (hPDLCs) were co-cultured with human peripheral blood mononuclear cells (hPBMCs) with the presence or absence of leptin. Small interfering RNA (siRNA) was transfected to knock down the leptin receptor (LepR). The mRNA expressions of the targeted genes were evaluated by quantitative real-time polymerase chain reaction. We found that leptin receptors were expressed on both rat periodontal ligament cells and hPDLCs. OTM was significantly attenuated in the leptin-treated group comparing to the control group. The number of osteoclasts was reduced in the periodontal ligament tissues and co-cultured system when treated with leptin. The expression of RANKL was inhibited by leptin administration either and . Leptin administration also inhibited the force-induced up-regulation of RANKL expression in hPDLCs, which was rescued by LepR siRNA transfection. The osteoclastogenesis was attenuated by leptin administration which was reversed by the LepR siRNA transfection. Taken together, leptin was able to attenuate OTM by inhibiting osteoclastogenesis which can be attributed to the reduced expression of RANKL in the periodontal ligament. Leptin may possess the potential for reinforcing anchorage clinically.
本研究旨在探讨多功能激素瘦素对正畸牙齿移动（OTM）的影响及其潜在机制。建立了Sprague-Dawley大鼠OTM模型，并分为两组，分别给予赋形剂或瘦素。使用体视显微镜和微型计算机断层扫描来评估OTM的量。采用抗酒石酸酸性磷酸酶（TRAP）染色、免疫组织化学和免疫荧光染色来检测破骨细胞和相关蛋白表达。施加压缩力后，将人牙周膜细胞（hPDLCs）与存在或不存在瘦素的人外周血单核细胞（hPBMCs）共培养。转染小干扰RNA（siRNA）以敲低瘦素受体（LepR）。通过定量实时聚合酶链反应评估靶向基因的mRNA表达。我们发现瘦素受体在大鼠牙周膜细胞和hPDLCs上均有表达。与对照组相比，瘦素处理组的OTM明显减弱。用瘦素处理时，牙周膜组织和共培养系统中的破骨细胞数量减少。瘦素给药也抑制了RANKL的表达。瘦素给药还抑制了hPDLCs中力诱导的RANKL表达上调，而LepR siRNA转染可挽救这种上调。瘦素给药减弱了破骨细胞生成，而LepR siRNA转染可逆转这种情况。综上所述，瘦素能够通过抑制破骨细胞生成来减弱OTM，这可能归因于牙周膜中RANKL表达的降低。瘦素在临床上可能具有增强支抗的潜力。
