While several signaling pathways including integrin, NF-κB, and Src could be involved in regulating osteoclast function (14), we focused on small GTPase Rac/Cdc42 signaling pathways since previous studies showed that double KO of Rac1 and Rac2 in mice caused osteopetrosis due to cytoskeleton disarrangement and osteoclast dysfunction (8, 38). This evidence concerns the gene CDC42 and osteopetrosis.