Semaphorins in Bone Development, Homeostasis, and Disease

Semaphorins were originally identified as axon guidance cues in the development of the nervous system. In recent years, numerous studies have determined that they are also involved in organogenesis, vascularization/angiogenesis, oncogenesis, and immune responses. In addition, the mechanisms underlying the diverse functions of semaphorins and their receptors have been identified. Recently, significant advances have been made in our understanding of the roles of semaphorins in bone remodeling, particularly the regulation of osteoclast and osteoblast differentiation and migration. Moreover, dysregulated semaphorin expression causes severe bone diseases, including osteoporosis and osteopetrosis. This review focuses on advanced findings on the role of semaphorins/receptors and their intracellular signaling in the regulation of bone homeostasis.