Eph Receptors and Ephrin Signaling Pathways: A Role in Bone Homeostasis

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.

Measles virus nucleocapsid protein increases osteoblast differentiation in Paget’s disease

“…As expected, EphB4-Fc blocked OB differentiation ( Figure 3C) and suppressed OCL differentiation by inhibiting the c-Fos/NFATc1 cascade (Figure 3, D-F), as reported in other models (16). Interestingly, EphB4-Fc treatment also decreased IL-6 and IGF1 expression in these cocultures.…”

“…We found that IL-6 (10 ng/ml) also increased ephrinB2 expression on OCLs derived from CD11b + cells from WT mice ( Figure 4D) as well as EphB4 expression in WT OBs ( Figure 4F). Interestingly, IL-6 only induced ephrinB2 expression in MVNP-transduced human OCLs (Figure 4E), suggesting that another factor induced by MVNP cooperates with IL-6 to increase ephrinB2 expression in receptors promote skeletal development (16). Zhao and coworkers showed that bidirectional ephrinB2/EphB4 signaling regulates bone remodeling (15), that OCLs express the NFATc1 target gene ephrinB2 and OBs express its receptor EphB4, and that transgenic mice with increased EphB4 signaling in OBs had enhanced bone mass (15).…”

“…Eph receptor expression on OBs and ephrins on OCLs and OBs have been implicated as major regulators of coupling (15). Ephs and ephrins are cell-surface molecules that signal bidirectionally and play major roles in tumor progression, angiogenesis, cell migration, and morphogenesis (16). Irie et al reported that bidirectional signaling through ephrinA2/EphA2 enhances osteoclastogenesis and suppresses OB differentiation (17).…”

microRNA Expression in Rat Apical Periodontitis Bone Lesion

“…blast lineage cells) and the bone-resorbing osteoclasts, a process namely bone remodeling. The balance between the two activities is under the spatio-temporal control of several signaling pathways (1)(2)(3)(4)(5). Any interrupttion of the balance between osteoblasts and osteoclasts can compromise bone remodeling.…”

Alendronate Affects Osteoblast Functions by Crosstalk through EphrinB1-EphB

“…Cell-surface molecules, such as receptors and their associated ligands, play a role in the maintenance of bone homeostasis (Edwards and Mundy, 2008). EphrinB2 and EphB4 mediate osteoclast-osteoblast interactions by simultaneous signal transduction in both cells.…”