Wnt signaling pathway as a regulator of bone formation and healing

Abstract

Bone is a mineralized structure that is mainly made of a matrix that supports the various types of bone cells;  osteoblasts, osteoclasts, osteocytes and bone lining cells. Bone mass is preserved as a result of the balance between  bone forming osteoblasts and bone resorbing osteoclasts, in a process known as bone remodeling. Bone remodeling  process occurs mainly in three steps: resorption, reversal and formation. These steps are controlled locally and  systemically by numerous regulatory factors. Among these regulatory factors, wingless-related MMTV integration site  (Wnt) signaling pathway plays a significant role in maintainig bone mass as well as regulating many cellular processes.  Based on whether β-catenin is involved or not, Wnt signaling is categorized into two main pathways; the canonical and  the non-canonical pathways. The actions exerted by the Wnt signaling pathway are achieved when Wnt ligands bind to specific transmembrane receptors such as the Frizzled family (Frz) members and low density lipoprotein receptor- related proteins (LRPs) and are inhibited when these ligands or receptors bind to Wnt signaling inhibitors such as Wnt  inhibitory factor 1 (WIF1), secreted Frizzledrelated proteins (sFRPs), Dickkopf 1 (DKK1) and sclerostin. Improper synthesis  of any of these ligands, receptors or inhibitors leads to disruption of different body functions and progression  of various diseases including skeletal diseases. Therefore, the components of the Wnt signaling pathway  can be targeted for developing novel therapeutic agents to manage different diseases.