交感神经系统调控正畸牙齿移动机制的研究

Sympathetic nervous system (SNS) may regulate skeletal homeostasis. However, it is unknown whether SNS contributes to orthodontic tooth movement (OTM). In this study, we revealed that SNS activation by β-adrenergic receptor agonist isoproterenol (ISO) treatment accelerated OTM in mouse model. In contrast, sympathectomy of superior cervical ganglion ectomy (SCGx) reduced OTM, suggesting that SNS regulates mechanical force-induced OTM. Moreover, we used histopathological analysis to show that compressive region of periodontal ligament (PDL) has increased number of β2-adrenergic receptor (Adrb2) positive cells after application of orthodontic force. We further confirmed that periodontal ligament cells (PDLSCs) expressed Adrb2 and, more importantly, the expression levels of Adrb2 in PDLSCs were upregulated by mechanical force through increase of intracellular Ca2+ concentration ([Ca2+]i). Next, we determined that activation of Adrb2 in PDLSCs promoted osteoclastogenesis via elevating RANKL/OPG ratio in a PDLSCs-PBMCs coculture system and an in vivo mouse model. We further used Adrb2-/- mice to confirm that Adrb2 is required for orthodontic force-induced osteoclasts differentiation. In summary, this study suggests that mechanical force-induced Adrb2 expression in PDLSCs contributes to SNS-regulated OTM.

牙槽骨改建是正畸牙齿移动（OTM）关键过程，交感神经系统（SNS）及β2-肾上腺素受体（Adrb2）在骨改建中发挥重要作用，然而SNS是否调节OTM尚不明确，机械力刺激如何调控牙槽骨改建也尚无定论。本研究拟建立正畸加力动物模型，注射β受体激动剂及切除颈上交感神经节，观察其对OTM的影响，正反向验证SNS能否调节OTM；观察OTM前后牙周膜Adrb2表达与分布的变化。分离培养鉴定人PDLSCs,验证其Adrb2表达，探讨机械力刺激是否通过调节钙离子内流调控Adrb2表达及活性。并探讨PDLSCs中Adrb2是否通过RANKL/OPG促进破骨细胞形成。最后利用Adrb2-/-小鼠进一步确认Adrb2在OTM中的调控作用。综上，本研究将探讨SNS是否通过PDLSCs中Adrb2调控机械力介导的OTM及其机制,这将为理解OTM的分子生物学调控机制及临床干预OTM提供新的理论基础与实验依据。

牙槽骨改建是正畸牙齿移动（OTM）关键过程，交感神经系统（SNS）及β2-肾上腺素受体（Adrb2）在骨改建中发挥重要作用，然而SNS是否调节OTM尚不明确，机械力刺激如何调控牙槽骨改建也尚无定论。本研究建立了正畸加力动物模型，通过注射β受体激动剂及切除颈上交感神经节，发现β受体激动剂可以加快OTM，而颈上交感神经节切除会减慢OTM，在动物模型中正反向验证了SNS可以调节OTM；发现了OTM中，加力后前后牙周膜Adrb2表达上升。通过分离培养鉴定人PDLSCs,验证了其Adrb2表达，探械力刺激可以通过调节钙离子内流调控Adrb2的表达。此外PDLSCs中Adrb2可以通过调节RANKL/OPG而影响破骨细胞形成。最后利用Adrb2-/-小鼠的正畸加力模型，发现缺乏Adrb2会使正畸牙移动减慢，破骨细胞减少，进一步确认了SNS在OTM中的调控作用。此外，进一步的研究发现不仅SNS，免疫系统以及小分子气体也会参与到正畸牙移动的过程中。综上，本研究发现了SNS可以通过PDLSCs中Adrb2调控机械力介导的OTM及其可能机制,而且提示正畸牙移动是涉及到全身系统变化复杂生物学过程，这将为理解OTM的分子生物学调控机制及临床干预OTM提供新的理论基础与实验依据。