10 July 2024 | Lifang Hu, Wei Chen, Airong Qian, Yi-Ping Li
This review article provides an updated overview of the Wnt/β-catenin signaling pathway and its components, mechanisms, and roles in bone formation, homeostasis, and diseases. Wnt proteins, which are secreted and lipid-modified, bind to receptors on the cell surface to activate canonical or non-canonical Wnt signaling pathways. The canonical pathway, also known as the Wnt/β-catenin pathway, involves the activation of β-catenin, a key transcriptional co-activator, leading to the regulation of target genes. The non-canonical pathways, including the Wnt/planar cell polarity (PCP) and Wnt/calcium (Ca2+) pathways, are β-catenin-independent and play crucial roles in tissue development and homeostasis.
The article discusses the Wnt signaling pathway's components, including Wnt proteins, receptors, activators, and inhibitors, and their interactions with other signaling pathways such as Notch, Hedgehog, TGF-β/BMP, PTH, and estrogen signaling. It highlights the importance of Wnt signaling in bone formation, where it regulates the differentiation of bone marrow mesenchymal stem cells (BM-MSCs) into osteoblasts, and in bone homeostasis, where it maintains the balance between bone formation and resorption. The review also explores the therapeutic potential of targeting Wnt signaling to treat bone diseases, including the use of extracellular molecules, cytosolic components, and nuclear components of the Wnt signaling pathway.
Finally, the article evaluates key questions in Wnt signaling that require further investigation, emphasizing the importance of new biological analytical technologies in advancing our understanding of this conserved and versatile signaling pathway.This review article provides an updated overview of the Wnt/β-catenin signaling pathway and its components, mechanisms, and roles in bone formation, homeostasis, and diseases. Wnt proteins, which are secreted and lipid-modified, bind to receptors on the cell surface to activate canonical or non-canonical Wnt signaling pathways. The canonical pathway, also known as the Wnt/β-catenin pathway, involves the activation of β-catenin, a key transcriptional co-activator, leading to the regulation of target genes. The non-canonical pathways, including the Wnt/planar cell polarity (PCP) and Wnt/calcium (Ca2+) pathways, are β-catenin-independent and play crucial roles in tissue development and homeostasis.
The article discusses the Wnt signaling pathway's components, including Wnt proteins, receptors, activators, and inhibitors, and their interactions with other signaling pathways such as Notch, Hedgehog, TGF-β/BMP, PTH, and estrogen signaling. It highlights the importance of Wnt signaling in bone formation, where it regulates the differentiation of bone marrow mesenchymal stem cells (BM-MSCs) into osteoblasts, and in bone homeostasis, where it maintains the balance between bone formation and resorption. The review also explores the therapeutic potential of targeting Wnt signaling to treat bone diseases, including the use of extracellular molecules, cytosolic components, and nuclear components of the Wnt signaling pathway.
Finally, the article evaluates key questions in Wnt signaling that require further investigation, emphasizing the importance of new biological analytical technologies in advancing our understanding of this conserved and versatile signaling pathway.