Bidirectional ephrin signaling in bone

Abstract

The interaction between ephrin ligands (efn) and their receptors (Eph) is capable of inducing forward signaling, from ligand to receptor, as well as reverse signaling, from receptor to ligand. The ephrins are widely expressed in many tissues, where they mediate cell migration and adherence, properties that make the efn-Eph signaling critically important in establishing and maintaining tissue boundaries. The efn-Eph system has also received considerable attention in skeletal tissues, as ligand and receptor combinations are predicted to mediate interactions between the different types of cells that regulate bone development and homeostasis. This review summarizes our current understanding of efn-Eph signaling with a particular focus on the expression and functions of ephrins and their receptors in bone.

Keywords: Bone; Ephrins; Osteoblast; Osteoclast; Signaling.

Fig. 1

A model for ephrin ligand-receptor regulation of bone cell interaction in bone development and homeostasis. Several ephrin ligands and receptors mediate growth plate development during bone growth. Interactions between osteoblasts (OB), osteoclasts (OC), endothelial cells (EC) and chondrocytes are mediated by different ephrin ligand-receptor combinations, coordinating bone cell development and activity.

Fig. 2

Intracellular EphB/efnB signaling between osteoblast and osteoclast lineage cells in bone formation. Osteoblast development is mediated by forward signaling through EphB4 from efnB2 on osteoclasts and reverse signaling through efnB1 from EphB receptor on MSC. NERFH1 dephosphorylates TAZ for localization to the nucleus. Osteoclast development is mediated by reverse signaling through efnB2 from EphB4 on osteoblasts. Dvl2, Dishevelled2; MSC, mesenchymal stromal cells; NHERF, Na/H exchange regulatory factor; TAZ-P, phosphorylated TAZ.