| As a very conservative signal transduction pathway, WNT signal pathway has high degree of homology among all the family members from lower animals (such as drosophila melanogaster) to higher mammals. It mainly can be divided into three pathways:(1) Wnt/β-catenin signal pathway, that is classical Wnt pathway(2) Wnt/PCP (Planar Cell Polarity) signal pathway(3) Wnt/Ca2+signal pathway. Wnt signal pathway plays an important role in regulation in the physiological processes of cell differentiation, proliferation, apoptosis as well as in the pathwayological processes such as cell canceration, tumor invasion, and so on. Therefore, There is substantial knowledge on the signaling cascade downstream to Wnt stimulation; however, the control of production of Wnt proteins has remained an essentially uncharted territory.Moreover, the study of Wnt signal pathway, especially classical Wnt pathway, has a significant meaning to the study of oral medicine. The Wnt signal pathway is activated, not only β-Catenin intranuclear accumulation is one kind of general feature of oral cavity squamous cell carcinoma, but also Wnt signal pathway is recognized as a significant signal system that has a guiding effect on the formation and differentiation of patterns in the development process of the embryo and organs. Wnt signal system takes part in the development of oral and maxillofacial organs such as maxillofacial development, dental germ development, the morphogenesis of teeth and so on. In addition, classical Wnt signal pathway, as a fairly critical pathway in osteogenic differentiation, is good for improving the knowledge about the facial osteogenesis of chin when it come to the study on Wnt classic pathway, and it offers theoretical bases for solving bone defect caused by mouth neoplasm, facial wounds of chin and periodontal diseases.However, the previous researches always focus on influencing the osteogenesis signal channel and stimulating osteanagenesis through chemical micro-molecule and cell factor. Although many studies proved that small molecules and cell factors could activate the signal pathway of osteogenesis, the price of these artificially synthesized cell factors is high and cell factors tend to reach the whole body along with blood and it is difficult to activate osteogenesis at a fixed position. Moreover, the concentration of these small molecules or cell factors would decrease over time and it is difficult to fixedly and enduringly induce the signal pathway of osteogenesis. While the mechanics signal is greatly different, compared with the cell factor, it can produce much more everlasting mechanics signal to induce osteogenesis. Therefore, it has more research value to activate the Wnt signaling pathway by the mechanical signal. Our previous experiments shows that in the relatively hard extracellular matrix, β-Catenin can not only accumulate under the stimulating of the signal of WNT, but also can translocate into the nucleus, which itself may also induce the expression of WNT proteins, suggesting that there may exist a regulatory role of positive feedback in the WNT/p-Catenin pathway.This topic will discuss the positive-feedback molecular mechanism of Wnt gene which is adjusted by P-Cateninin WNT/β-Catenin, and make use of information biology, molecular cloning technology, luciferase reporter gene technology and point mutation technology to respectively construct the promoter region of Wnt1, the promoter region mutant of Wnt1and the luciferase reporter gene plasmid of promoter region in Wnt3a, and determined that β-Catenin can combine with Wntl and Wnt3a using dual-luciferase reporter gene technique, and found the binding site of Wntl and β-Catenin, which is probably the molecular mechanism of positive feedback control of WNT/β-Catenin pathway under the elasticity of the extracellular matrix. |
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