The Role Of BMP Type ? Receptor ACVR1 In The Development Of Dentin And The Periodontium

Various external stimuli,such as caries and trauma,can destroy the normal tissue of the teeth,leading to the defect or loss of the tooth,and then affect the function of chewing and pronunciation.The dentin,as the main component of the tooth,plays an important role in protecting the dental pulp against external stimuli.Therefore,the study of dentin development provides a theoretical basis for the promotion of dentin regeneration.BMP signaling pathway plays an important role in odontoblast differentiation and dentin formation.However,there is little research on the role of BMP type I receptor ACVR1 in the regulation of dentin formation.In this experiment,the effect of ACVR1 on the formation of dentin in mice was observed by Osterix-Cre and Acvr1 conditional gene knockout mice.The role of ACVR1 in the formation of the dentin of the incisor and molar teeth of mice was observed at the same time.Micro-CT results showed that at PN21,the mandible in the knockout group was smaller than the control group and the salinity decreased,and the incisors in the knockout group were smaller than the control groupand formed discontinuous hard tissues.HE staining showed that there was no significant difference between molars in the knockout group and the control group at PN5.When compared with the control group,the molars in the knockout group were shorter,the pulp cavity enlarged,the dentin thickness became thinner,and the predentin thickness increased in the PN21 group.At PN5,the osteoid dentin formation was found in the incisor of the knockout group of mice,and the obvious osteodentin formation was still visible in the knockout group at PN21.Real time quantitative RT-PCR detection of odontogenic / osteogenic genes showed that in molars,knockout tooth related genes(Col1,Dmp1,Dsp,Nestin,Sp7)showed no difference with the control group,while the osteogenic related gene(Bsp)was significantly up-regulated.Immunohistochemical staining and quantitative analysis to confirm this the results found that osteogenic gene BSP in knockout in predentin have significantly positive signal,while negative in the knockout group of molar dentin and the control group of molar dentin,predentin had no expression.In the incisors,real-time quantitative RT-PCR results showed that compared with the control group,the Dsp expression of the odontogenic related genes in the knockout group was down regulated,and the expression of osteogenic related gene Bsp was upregulated.Real time quantitative RT-PCR was used to detect the Wnt pathway in incisor and molar.Theresults showed that the expression of WNT inhibitor Dkk1 and Sost in the knockout group was lower than that in the control group,while the expression of Dkk1 and Sost in the knockout molar was not different from that in the control molars.Therefore,this chapter puts forward the different functions of ACVR1 in mouse incisors and molars that ACVR1 promotes mouse molar tooth formation and inhibits osteodentin formation in mouse incisors.In addition,it is suggested that WNT may be an important signal pathway for ACVR1 to regulate the differentiation of mesenchymal cells into odontoblasts.Periodontal as a supporting tissue of tooth plays an important role in maintaining the physiological function of teeth and slowing down the masticatory pressure.Therefore,by knocking out the Acvr1,we can clarify the role of ACVR1 in periodontal tissue(alveolar bone,cementum and periodontal ligament).By Micro-CT,HE staining and immunohistochemical method,we found that in mesenchymal Acvr1 knockout alveolar bone,trabecular thicknes,bone mineral density and tissue mineral density were decreased by the decreased activity of osteoblasts and increased osteoclast activity induced by increased RANKL/OPG signaling from osteoblasts to osteoclasts.After Acvr1 was knocked out,there was almost no effect on the formation of cementum,and the expression of Col1 and BSP in cementoblasts was almostunchanged.In addition,Acvr1 knockout group led to periodontal ligament fiber disorder and irregular vascular morphology.Fibroblast differentiation related factors Col1 and Nestin were weakened in the c KO group.It is suggested that ACVR1 is important for the formation of periodontal tissue,especially for the formation of alveolar bone.It is suggested that ACVR1 in osteoblasts inhibit osteoclasts through RANKL/OPG,and promotes osteogenesis.