RAC1 and osteopetrosis: 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).