The role of Src-p130Cas axis in osteoclastic bone resorption

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Osteoclast-specific p130Cas conditional knockout mice (p130Cas cKO) exhibit a high bone mass phenotype caused by defect in multinucleation and cytoskeleton organization causing bone resorption deficiency. Bone marrow cells from p130Cas cKO were able to differentiate into osteoclasts and wild-type cells in vitro. However, osteoclasts from p130Cas cKO failed to form actin rings and resorb pits on dentine slices. Although the initial events of osteoclast attachment were intact, the Rac1 activity that organizes the actin cytoskeleton was reduced, and its distribution was disrupted in p130Cas cKO osteoclasts. Dedicator of cytokinesis 5 (Dock5), a Rho family guanine nucleotide exchanger, failed to associate with Src or Pyk2 in osteoclasts in the absence of p130Cas. These results strongly indicate that p130Cas plays pivotal roles in osteoclastic bone resorption