Non-canonical Wnt signals regulate cytoskeletal remodeling in osteoclasts

Osteoclasts are multinucleated cells responsible for bone resorption. Osteoclasts adhere to the bone surface through integrins and polarize to form actin rings, which are formed by the assembly of podosomes. The area contained within actin rings (also called sealing zones) has an acidic pH, which causes dissolution of bone minerals including hydroxyapatite and the degradation of matrix proteins including type I collagen by the protease cathepsin K. Osteoclasts resorb bone matrices while moving on bone surfaces. Osteoclasts change their cell shapes and exhibit three modes for bone resorption: motile resorbing mode for digging trenches, static resorbing mode for digging pits, and motile non-resorbing mode. Therefore, the actin cytoskeleton is actively remodeled in osteoclasts. Recent studies have revealed that many molecules, such as Rac, Cdc42, Rho, and small GTPase regulators and effectors, are involved in actin cytoskeletal remodeling during the formation of actin rings and resorption cavities on bone slices. In this review, we introduce how these molecules and non-canonical Wnt signaling regulate the bone-resorbing activity of osteoclasts.