EphrinB2 Signalling in Osteoblast Differentiation, Bone Formation and Endochondral Ossification

Abstract

The main functions of the osteoblast lineage (pre-osteoblasts, osteoblasts and osteocytes) are the production of bone matrix (osteoid), its mineralisation and the support of osteoclast formation. EphrinB2 and its contact-dependent re-ceptor, EphB4, are stably expressed through all these stages of the lineage, and their expression of ephrinB2 is stimulated by parathyroid hormone (PTH), an agent that stimulates bone formation. Recent work has shown that the ephrinB2/EphB4 interaction is required for late stages of osteoblast differentia-tion and PTH action. Furthermore, specific deletion of ephrinB2 within the osteoblast lineage delays the process of bone mineralisation resulting in impaired bone strength and its response to anabolic PTH in both trabecular and periosteal bone. EphrinB2 and EphB4 are also expressed in growth plate chondrocytes, cells that also support osteoclast formation in development and fracture healing. This review will discuss the roles of forward and reverse signalling through EphB4 and ephrinB2, respectively, in bone growth and remodelling.