| Bone is a unique organ formed of dense, mineralized connective tissue that is formed and regulated by osteoclasts and osteoblasts. The aim of this study was to identify the role of Rac 1 and Rac 2 on osteoclastogenesis. Murine bone marrow cells and peritoneal macrophages, with the targeted deletion of Rac 1 and Rac 2 genes, were cultured in the presence of sRANKL and M-CSF. In vitro osteoclastogenesis, actin pyrene incorporation, spreading, and migration, were investigated. Commensurate with the impaired formation of osteoclasts, actin polymerization was impeded with Rac deletions, as was spreading and migration, while expression of the osteoclast markers TRAP and cathepsin K was delayed. These studies, therefore, demonstrate that the small GTPases Rac 1 and Rac 2, through their effects on cytoskeletal remodelling, are critically involved in M-CSF and RANKL induced osteoclastogenesis. Rac 1 plays a more significant role than Rac 2 in the early phases of osteoclast formation, prior to precursor fusion. |
