Mechanoactivation of Wnt/β-catenin pathways in health and disease

Mechanical forces play an important role in regulating tissue development and homeostasis in multiple cell types including bone, joint, epithelial and vascular cells, and are also implicated in the development of diseases, e.g. osteoporosis, cardiovascular disease and osteoarthritis. Defining the mechanisms by which cells sense and respond to mechanical forces therefore has important implications for our understanding of tissue function in health and disease and may lead to the identification of targets for therapeutic intervention. Mechanoactivation of the Wnt signalling pathway was first identified in osteoblasts with a key role for β-catenin demonstrated in loading-induced osteogenesis. Since then, mechanoregulation of the Wnt pathway has also been observed in stem cells, epithelium, chondrocytes and vascular and lymphatic endothelium. Wnt can signal through both canonical and non-canonical pathways, and evidence suggests that both can mediate responses to mechanical strain, stretch and shear stress. This review will discuss our current understanding of the activation of the Wnt pathway in response to mechanical forces.