Expression, localisation and functional analysis of cytoskeletal motor proteins in bone resorbing osteoclasts

[Truncated abstract] Osteoclasts are terminally differentiated, multinucleated cells of the monocytemacrophage lineage, exclusively responsible for the physiological and pathological destruction of mineralised bone. During bone resorption, osteoclasts adopt a polarised conformation characterised by the development of three distinct membrane domains: 1) the sealing zone; 2) the basolateral functional secretory domain and perhaps most characteristic, 3) the bone-apposed ruffled border membrane, which functions as the osteoclasts’ bone resorbing organelle.

To achieve this, the osteoclast possesses a specialised cytoskeleton that is
unique amongst all eukaryotic cells. Unlike other cell types, the osteoclast cytoskeleton must be highly dynamic in order to fulfill cyclical requirements for motility and the generation of a polarised phenotype. Along with sustaining structural integrity, the osteoclast cytoskeleton also plays an important role in facilitating trafficking and motility of membrane-delimited intracellular carrier vesicles to specific destinations, a process that is fundamental to its bone-resorbing activity.