Extracellular Matrix Elastic Regulation Wnt3a Phenotype Expression Of Articular Chondrocytes

Recent studies have demonstrated that extracellular matrix(ECM) stiffness has a major influence on regulating the phenotypes and behaviors of various cell types including terminal differentiation cells, cancer cells and stem cells. Chondrocyte differentiation and phenotypic maintaining are regulated by ECM stiffnesss, and involve a series of signal transduction processes.Literature confirmed elastic matrix can affect the Wnt signaling and downstream target gene transcription, translation further affect the behavior of the cells and a variety of biological functions. The expression of WNT family regulation and downstream signal has a key role in the development of the cartilage and bone. Especially, Wnt3 a is involved in the regulation of chondrogenesis and cartilage development both in vivo and in vitro. By activating ofβ-catenin-Tcf/Lef transcription, Wnt3 a induces dedifferentiation of chondrocytes. However, the regulatory factors of Wnt3 a expression and the chondrocyte phenotype maintaining pathway on deformable ECM remain unsolved.This study in biomechanics and cell biology researchers currently in most the problem of energy as a breakthrough point, through the clinical medicine is the most difficult to conquer in articular cartilage disease and the most hot cells in tissue engineering material adaptability towards the environment in which to combine these two aspects of issues. The present paperusing western blotting, Real time PCR, luciferase assay methods demonstrates that stiff substrates stimulate β-catenin accumuation, which binds to Wnt3 a promoter region and regulate Wnt3 a expression, thus induce Chondrocyte dedifferentiation. This study illustrates that ECM mechanical signals regulate the expression of Wnt3 a protein via a positive feedback loop, which plays an important role in Chondrocyte differentiation and phenotypic maintaining.Behind this phenomenon, we found that the β-catenin direct regulation effects of Wnt3 a,further enrich the regulation mechanism of Wnt3 a itself. In the study cell adhesion of tissue engineering materials and the extracellular matrix elastic characteristics of implant materials is of great significance, at the same time, the research on etiology of osseous joint disease not only basic research significance, also has important medical application prospect.