Abstract
There is growing evidence that osteopontin (OPN) plays an important role in cell migration, which is one of the key events in the immune response, and tumor metastasis and invasion. Although OPN is recognized generally as a secreted protein, we have shown the presence of an intracellular form of OPN (iOPN) in migrating fibroblasts, activated macrophages, motile osteoclasts and metastatic cells, which indicates the importance of iOPN in cell migration. In this study, we examined the effects of exogenous OPN on the impaired cell spreading and migration observed in OPN-null osteoclasts, to determine whether iOPN has functional significance in osteoclast motility. The results show that 1) in osteoclasts, generated from OPN-null bone marrow cells in the presence of M-CSF and RANKL, cell spreading and protrusion of pseudopodia were reduced and cell fusion was impaired, which resulted in smaller osteoclasts with fewer nuclei, 2) osteoclast migration towards M-CSF was significantly compromised in OPN-null mice, and 3) exogenous OPN, which was pre-coated onto the TranswellTM membrane, failed to restore the impaired osteoclast spreading and migration observed in the OPN-null mice. These findings have identified an intracellular form of OPN that appears to function in the migration and fusion of osteoclasts.
