Cytoskeletal dysfunction dominates in DAP12-deficient osteoclasts.

ABSTRACT: Despite evidence that DAP12 regulates osteoclasts, mice lacking the ITAM-bearing protein exhibit only mild osteopetrosis. Alternatively, Dap12(-/-) mice, also lacking FcRgamma, are severely osteopetrotic, suggesting that FcRgamma compensates for DAP12 deficiency in the bone-resorbing polykaryons. Controversy exists, however, as to whether these co-stimulatory molecules regulate differentiation of osteoclasts or the capacity of the mature cell to degrade bone. We find that Dap12(-/-) osteoclasts differentiate normally when generated on osteoblasts but have a dysfunctional cytoskeleton, impairing their ability to transmigrate through the osteoblast layer and resorb bone. To determine whether the FcRgamma co-receptor, OSCAR mediates osteoclast function in the absence of DAP12, we overexpresse

SUBMITTER: Zou W 

PROVIDER: S-EPMC2923570 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature