Roles of Wnt/β-catenin signaling in adipogenic differentiation potential of adipose-derived mesenchymal stem cells

Abstract: Wnt/β-catenin signaling pathway controls differentiation of various cells by regulating the expression of target genes. β-Catenin plays a central role in Wnt/β-catenin signaling pathway. To investigate the molecular mechanisms of fate determination in adipose-derived mesenchymal stem cells (AMSCs), we investigated effects of Wnt3a and β-catenin, two key members of the Wnt/β-catenin signaling, in adipogenic differentiation of porcine AMSCs. We demonstrated that Wnt3a protein can inhibit the adipogenic differentiation of porcine AMSCs in vitro culture. By stabilization of cytoplasmic β-catenin with continuous treatment by LiCl, the adipogenic differentiation of AMSCs was also suppressed and the osteogenesis was stimulated. In contrast, a loss of β-catenin in AMSCs enhanced the adipogenic differentiation and rescued LiCl-induced anti-adipogenesis. In addition, the mutual activation of CCAAT/enhancer-binding protein-α (C/EBPα) and peroxisome proliferator-activated receptor-γ (PPARγ) were repressed in the presence of Wnt3a or LiCl, but increased in the gene silencing of β-catenin. Taken together, our study indicated that Wnt/β-catenin signaling pathway inhibited the adipogenic differentiation potential and alter the cell fate from adipocytes to osteoblasts. [Copyright &y& Elsevier]