Abstract:
The transforming growth factor β (TGFβ) superfamily is a master regulator of development, adult homeostasis, and wound repair. Dysregulated TGFβ signaling can lead to cancer, fibrosis, and musculoskeletal malformations. We previously demonstrated that TGFβ receptor 2 (Tgfbr2) signaling regulates odontoblast differentiation, dentin mineralization, root elongation, and sensory innervation during tooth development. Sensory innervation also modulates the homeostasis and repair response in adult teeth. We hypothesized that Tgfbr2 regulates the neuro-pulpal responses to dentin injury. To test this, we performed a shallow dentin injury with a timed deletion of Tgfbr2 in the dental pulp mesenchyme of mice and analyzed the levels of tertiary dentin and calcitonin gene-related peptide (CGRP) axon sprouting. Microcomputed tomography imaging and histology indicated lower dentin volume in Tgfbr2cko M1s compared to WT M1s 21 days post-injury, but the volume was comparable by day 56. Immunofluorescent imaging of peptidergic afferents demonstrated that the duration of axon sprouting was longer in injured Tgfbr2cko compared to WT M1s. Thus, CGRP+ sensory afferents may provide Tgfbr2-deficient odontoblasts with compensatory signals for healing. Harnessing these neuro-pulpal signals has the potential to guide the development of treatments for enhanced dental healing and to help patients with TGFβ-related diseases.
摘要:
转化生长因子β(TGFβ)超家族是发育的主要调控因子,成人稳态,和伤口修复。TGFβ信号传导失调可导致癌症,纤维化,肌肉骨骼畸形.我们先前证明TGFβ受体2(Tgfbr2)信号调节成牙本质细胞分化,牙本质矿化,根伸长,和牙齿发育过程中的感觉神经支配。感觉神经支配还调节成人牙齿的体内平衡和修复反应。我们假设Tgfbr2调节神经髓对牙本质损伤的反应。为了测试这个,我们对小鼠牙髓间质中的Tgfbr2进行了浅牙本质损伤,并分析了三级牙本质和降钙素基因相关肽(CGRP)轴突发芽的水平。显微计算机断层扫描成像和组织学显示,与受伤后21天的WTM1s相比,Tgfbr2ckoM1s的牙本质体积较低,但是到第56天的音量相当。肽能传入的免疫荧光成像表明,与WTM1s相比,受伤的Tgfbr2cko轴突发芽的持续时间更长。因此,CGRP感觉传入可能为Tgfbr2缺陷的成牙本质细胞提供代偿信号以进行愈合。利用这些神经牙髓信号有可能指导改善牙齿愈合的治疗方法的发展,并帮助患有TGFβ相关疾病的患者。