Abstract：
Primary failure of eruption (PFE) is a rare disorder that is characterized by the inability of a molar tooth/teeth to erupt to the occlusal plane or to normally react to orthodontic force. This condition is related to hereditary factors and has been extensively researched over many years. However, the etiological mechanisms of pathogenesis are still not fully understood. Evidence from studies on PFE cases has shown that PFE patients may carry parathyroid hormone 1 receptor (PTH1R) gene mutations, and genetic detection can be used to diagnose PFE at an early stage. PTH1R variants can lead to altered protein structure, impaired protein function, and abnormal biological activities of the cells, which may ultimately impact the behavior of teeth, as observed in PFE. Dental follicle cells play a critical role in tooth eruption and root development and are regulated by parathyroid hormone-related peptide (PTHrP)-PTH1R signaling in their differentiation and other activities. PTHrP-PTH1R signaling also regulates the activity of osteoblasts, osteoclasts and odontoclasts during tooth development and eruption. When interference occurs in the PTHrP-PTH1R signaling pathway, the normal function of dental follicles and bone remodeling are impaired. This review provides an overview of PTH1R variants and their correlation with PFE, and highlights that a disruption of PTHrP-PTH1R signaling impairs the normal process of tooth development and eruption, thus providing insight into the underlying mechanisms related to PTH1R and its role in driving PFE.
摘要：
原发性萌出失败（PFE）是一种罕见的疾病，其特征是磨牙/牙齿无法萌出咬合平面或无法正常对正畸力作出反应。这种情况与遗传因素有关，并且已经进行了多年的广泛研究。然而,发病机理的病因机制尚不完全清楚。来自PFE病例研究的证据表明，PFE患者可能携带甲状旁腺激素1受体（PTH1R）基因突变，基因检测可用于早期诊断PFE。PTH1R变体可以导致改变的蛋白质结构，受损的蛋白质功能，细胞的异常生物活性，这最终可能会影响牙齿的行为，在PFE中观察到。牙囊细胞在牙齿萌出和牙根发育中起关键作用，并在其分化和其他活动中受到甲状旁腺激素相关肽（PTHrP）-PTH1R信号传导的调节。PTHrP-PTH1R信号还调节成骨细胞的活性，在牙齿发育和萌出期间的破骨细胞和齿状细胞。当PTHrP-PTH1R信号通路发生干扰时，牙囊的正常功能和骨重塑受损。这篇综述概述了PTH1R变体及其与PFE的相关性，并强调PTHrP-PTH1R信号的中断会损害牙齿发育和萌出的正常过程，从而深入了解与PTH1R相关的潜在机制及其在驱动PFE中的作用。
