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.

Semaphorins and their receptor molecules actively participate in bone remodeling process. Understanding the role of semaphorins in bone homeostasis may provide the potential targets for development of new therapeutics for bone disorders.Figure optionsDownload as PowerPoint slideHighlights
► Semaphorins/receptors are critically involved in bone remodeling process.
► Sema4D is an essential coupling factor in regulation of bone formation.
► Sema6D-plexin-A1 axis control osteoclastogenesis.
► Sema3A has osteoprotective effect.