细胞外基质弹性调控Wnt3a表达影响关节软骨细胞表型维持

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. the expression of WNT family regulation and downstream signal has a key role in the development of the cartilage and bone. Especially，wnt3a is involved in the regulation of chondrogenesis and cartilage development both in vivo and in vitro. By activating of β-catenin-Tcf/Lef transcription, Wnt3a induces dedifferentiation of chondrocytes. However, the regulatory factors of Wnt3a expression and the chondrocyte phenotype maintaining pathway on deformable ECM remain unsolved. The present paper demonstrates that stiff substrates stimulate β-catenin accumuation, which binds to wnt3a promoter and regulate Wnt3a expression, thus induce Chondrocyte dedifferentiation. This study illustrates that ECM mechanical signals regulate the expression of Wnt3a protein via a positive feedback loop, which plays an important role in Chondrocyte differentiation and phenotypic maintaining.