Vimentin and actin interplay in the osteoclast life cycle

Abstract

Osteoclasts are large, multinucleated bone resorbing cells that partake in the process of bone remodelling, which is vital for skeletal growth, injury repair and overall bone homeostasis. They achieve their function through adhesion to substrate utilising actin-derived structures known as podosomes. Vimentin, on the other hand, is an intermediate filament known to partake in a multitude of cellular processes such as migration, wound healing, and structural support of the cell and its nucleus, and it has been shown to interact with the actin network. In this thesis, the effect of vimentin depletion in osteoclast podosome architecture, nuclear localisation and migration habits were investigated utilising osteoclasts derived from a vimentin-knockout mouse model. We show that vimentin alters the dynamics of different functional podosome structures, decreases the level of nuclear localisation and migration speed. Knockout osteoclasts also present with a phenotypic change, and fuse less often than their wildtype counterparts. Overall, these data suggest that vimentin does alter processes important to osteoclast function, and reveals a niche for further research.