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Review
. 2008 Sep 3;5(5):263-72.
doi: 10.7150/ijms.5.263.

Eph receptors and ephrin signaling pathways: a role in bone homeostasis

Claire M Edwards  1 , Gregory R Mundy
Affiliations
Review

Eph receptors and ephrin signaling pathways: a role in bone homeostasis

Claire M Edwards et al. Int J Med Sci. .

Abstract

The maintenance of bone homeostasis is tightly controlled, and largely dependent upon cellular communication between osteoclasts and osteoblasts, and the coupling of bone resorption to bone formation. This tight coupling is essential for the correct function and maintenance of the skeletal system, repairing microscopic skeletal damage and replacing aged bone. A range of pathologic diseases, including osteoporosis and cancer-induced bone disease, disrupt this coupling and cause subsequent alterations in bone homeostasis. Eph receptors and their associated ligands, ephrins, play critical roles in a number of cellular processes including immune regulation, neuronal development and cancer metastasis. Eph receptors are also expressed by cells found within the bone marrow microenvironment, including osteoclasts and osteoblasts, and there is increasing evidence to implicate this family of receptors in the control of normal and pathological bone remodeling.

Keywords: Bone remodeling; Eph receptors; coupling; ephrins; osteoblast; osteoclast.

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Conflict of interest statement

CONFLICT OF INTERESTS: The authors have declared that no conflict of interest exists.

Figures

Figure 1
Figure 1
Domain structure of Eph receptors and ephrinA and ephrinB ligands. Eph receptors have an extracellular region an ephrin-binding domain and two fibronectin type III repeats, and an intracellular region containing a tyrosine kinase domain, a SAM domain and a PDZ binding domain. EphrinA ligands are attached to the extracellular cell membrane with a GPI anchor. EphrinB ligands are transmembrane proteins with a cytoplasmic tail and PDZ binding domain. Bi-directional signaling results in forward signaling through Eph receptors and reverse signaling through ephrin ligands.
Figure 2
Figure 2
Proposed coupling of bone resorption and bone formation via EphB4 and ephrinB2. Zhao and collegues demonstrate expression of EphB4 on osteoblasts and ephrinB2 on osteoclasts. Forward signaling through EphB4 stimulates bone formation, whereas reverse signaling through ephrinB2 inhibits bone resorption . Therefore, the interaction between EphB4 and ephrinB2 results in a switch from resorption to formation.
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