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

Abstract

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.

Mechanotransduction and Adrenergic Stimulation in Arrhythmogenic Cardiomyopathy: An Overview of in vitro and in vivo Models

“…affected. Involvement of Wnt/β-catenin signaling in the pathogenesis of AC (Garcia-Gras et al, 2006) and the ability of mechanotransduction to activate canonical Wnt/β-catenin signaling (Warboys, 2018) was also confirmed in zebrafish. Furthermore, other authors demonstrated that YAP/TAZ play a central role in delivering information of mechanical environments surrounding cells to the nucleus transcriptional machinery suggesting a link between mechanotransduction and hippo pathway (Dobrokhotov et al, 2018).…”

CD93 negatively regulates astrogenesis in response to MMRN2 through the transcriptional repressor ZFP503 in the developing brain

“…Activated FAK phosphorylates AKT at Ser473, and AKT phosphorylates GSK3β at Ser9. β-Catenin is then free to translocate into the nucleus (43)(44)(45). To validate this signaling pathway, we measured protein levels.…”

Frizzled-4 regulates β-catenin in endothelial cells exposed to disturbed flow via an atypical Wnt pathway leading to proinflammatory activation and increased permeability

“…The Wnt signalling pathway is known to regulate responses to mechanical forces in non-vascular mechanoresponsive cells 8 . Transcriptomic analysis reveals that Wnt pathway genes are significantly enriched in EC exposed to atherogenic flow environments 9,10 suggesting a possible role in promoting flow-mediated EC dysfunction 10 .…”