**4.1 Wnt/β-catenin pathway**

The Wnt signaling pathway has an enormous vital role in the bone development and maintenance of bone homeostasis [33]. Wnt is a secreted protein ligand that

binds to a receptor complex of Frizzled (Fz) and low-density lipoprotein receptorrelated proteins (LRP). There are two modes of functioning for the Wnt proteins, i.e., canonical and non-canonical pathways, wherein the canonical pathway has a more specific role to play in the bone development. In the canonical pathway (**Figure 1**), the interaction of Wnt to the receptor complex hinders the functioning of axin, glycogen synthase kinase 3β (GSK-3β) and adenomatous polyposis coli (APC) protein. This primes the accumulation of β-catenin in the cytoplasm, further β-catenin travels down to the nucleus and ultimately stimulates lymphoid-enhancer-binding factor/Tcell-specific transcription factors (LEF/TCF). This results in the transcriptional activation for the genes that participate in bone formation and regeneration. While the absence of Wnt signal leads to phosphorylation of the cytosolic β-catenin and its subsequent ubiquitin-mediated degradation [34]. The degradation of the β-catenin finally turns off the downstream activation of the osteogenic genes. Accurate Wnt signaling is a pre-requisite for adequate bone mass in the body while mutation of the Wnt signaling components results in fractures and bone injuries [35].
