Rho GTPases in Bone and Tooth Development and Diseases

Rho GTPases—including RhoA, Rac1, and Cdc42—are key molecular switches that regulate cytoskeletal dynamics and transduce biochemical and mechanical signals essential for skeletal and dental tissue development. These small GTPases orchestrate fundamental cellular processes such as proliferation, migration, polarity, and differentiation, thereby guiding the morphogenesis, homeostasis, and regeneration of bone and teeth. In bone, Rho GTPases modulate osteoblast proliferation and matrix mineralization, osteoclast-mediated bone resorption, and mechanotransductive responses to physical stimuli. They are also critical for the behavior and fate specification of skeletal stem cells, integrating environmental cues to balance self-renewal and lineage commitment. In dental tissues, Rho GTPases regulate epithelial–mesenchymal interactions, odontoblast and ameloblast polarization, and the formation of enamel and dentin. Additionally, they play vital roles in craniofacial suture development, where their spatially and temporally controlled activity maintains suture patency and regulates ossification. Dysregulation of Rho GTPase signaling is implicated in a variety of pathological conditions, including osteoporosis, craniosynostosis, and dentinogenesis and amelogenesis imperfecta. Despite their therapeutic potential, targeting Rho GTPases remains challenging due to their pleiotropic functions and broad tissue distribution. This review highlights the mechanistic roles, regulatory networks, and developmental relevance of RhoA, Rac1, and Cdc42 in skeletal and dental biology, and discusses emerging strategies for modulating their activity in regenerative and disease contexts.