The Role Of SFrp2 And SFrp3 In Mouse Molar Development

Tooth is one of the common research model used in the study of the molecular mechanisms of organ development. Wnt signaling pathway is recognized as an imperative guiding signal system in the embryonic course of pattern formation and differentiation, it also plays a key role in the process of tooth development and differentiation. Secreted Frizzled-related protein (the secreted frizzled-related, sFRPs), known as functional regulation of soluble factors in the Wnt signaling, bind with the Frizzled membrane receptor through competition with Wnt ligands. Then Frizzled receptors will be isolated from Wnts ligands to block the classical and polarity pathway at the same time, which can achieve the antagonistic role of Wnt signaling. Existing research datas have confirmed that a variety of Wnt ligands and receptors and their regulatory factors have expressed in the developing and differentiation tooth germ. sFrp2 and sFrp3 had been found continuously expressing at E11.5-E13.5 molar tooth mesenchyme in our research. Clearly, this two kinds of factors has involved in the process of tooth development to regulate the Wnt signaling pathway. With the use of lentivirus-mediated RNAi technology, sFrp2 or sFrp3 expression has been reduced to approximately 20% compared with the original expression level at E13.5 mouse dental mesenchymal cells. However, sFrp2 and sFrp3 have dropped to over 15%, while Axin2 upregulates to 1.17 fold after 3-day's co-suppression of sFrp2 and sFrp3 in comparation to the original gene expression. When sFrp2 and sFrp3 were co-suppressed in 5 days, sFrp2 and sFrp3 have been declined by 77%,67% respectively compared to the control gene expression. Next, after the reorganization of the lentivirus infected mesenchymal cells aggregate with the E13.5 dental epithelium, implanted them under the mice kidney capsule for further development. The results showed that a single drop or increase of sFrp2 or sFrp3 does not affect tooth development and morphological differentiation. It is demonstrated that functional complementarity is evidently existed between sFrp2 and sFrp3. Yet, apparent tooth morphogenesis anomalies occurs in the sFrp2 and sFrp3 jointly-decreased mesenthyme. The ameloblast defferentiation has been blocked that result in impossible formation of enamel; odontoblast differentiation is abnormal and dentin secretion were significantly reduced; moreover, there is no enamel formation in the ultimate tooth. All in all, it is considered that sFrps plays a critical role.in the regulation of Wnt signaling pathway.