Eph–ephrin bidirectional signalling: A promising approach for osteoporosis treatment

Osteoporosis is a common disease characterised by low bone density and brittle bone due to osteoblast–osteoclast uncoupling. The cellular and molecular mechanisms responsible for osteoblast–osteoclast coupling lead to the identification of novel therapeutic targets. The increasing evidence for a role for Eph–ephrin signalling in biological processes, including cell–cell interactions, cell morphology, cell migration, angiogenesis, cancer and bone homeostasis, identifies new molecular pathways and potentially novel therapeutic targets for the treatment of diseases. Recent studies suggest that the interactions between Eph and ephrin play critical roles in bone cell differentiation and patterning by exerting dimorphic effects on osteoblast and osteoclast differentiation, resulting in the intriguing coupling of bone resorption and bone formation. These findings suggest that interventions targeting osteoblast–osteoclast coupling by the regulation of the Eph–ephrin bidirectional signalling according to its biological effects, which results in inhibiting osteoclastic resorption and promoting osteoblastic formation, may be a promising approach for osteoporosis prevention and treatment in the near future.