Abstract
Skeletal integrity is maintained through the tightly regulated bone remodeling process that occurs continuously throughout postnatal life to replace old bone and to repair skeletal damage. This is maintained primarily through complex interactions between bone resorbing osteoclasts and bone forming osteoblasts. Other elements within the bone microenvironment, including stromal, osteogenic, hematopoietic, endothelial and neural cells, also contribute to maintaining skeletal integrity. Disruption of the dynamic interactions between these diverse cellular systems can lead to poor bone health and an increased susceptibility to skeletal diseases including osteopenia, osteoporosis, osteoarthritis, osteomalacia, and major fractures. Recent reports have implicated a direct role for the Eph tyrosine kinase receptors and their ephrin ligands during bone development, homeostasis and skeletal repair. These membrane-bound molecules mediate contact-dependent signaling through both the Eph receptors, termed forward signaling, and through the ephrin ligands, referred to as reverse signaling. This review will focus on Eph/ ephrin cross-talk as mediators of hematopoietic and stromal cell communication, and how these interactions contribute to blood/ bone marrow function and skeletal integrity during normal steady state or pathological conditions.
Highlights
This review will focus on erythropoietin-producing human hepatocellular (Eph)/ ephrin cross-talk as mediators of hematopoietic and stromal cell communication, and how these interactions contribute to blood/ bone marrow function and skeletal integrity during normal steady state or pathological conditions
With the development of appropriate research tools including conditional knockout and transgenic mice, specialized in vitro culture systems, unique engineered substrates, soluble Eph and ephrin-Fc fusion proteins, Eph-ephrin inhibitory peptides and functional blocking antibodies, we have a greater understanding of how these cells interact within the bone through Eph-ephrin communication to maintain skeletal integrity
It is clear that the Eph-ephrin family members play a role in many vital biological processes during skeletal development and in maintaining skeletal physiology, where dysregulation can lead to a number of pathophysiological conditions within the musculoskeletal system
Summary
This review will focus on Eph/ ephrin cross-talk as mediators of hematopoietic and stromal cell communication, and how these interactions contribute to blood/ bone marrow function and skeletal integrity during normal steady state or pathological conditions. These observations suggest that ephrin-B2-expressing osteogenic cells are responsive to parathyroid hormone-related protein (PTHrP)/ PTH mediating homotypic interactions presumably with EphB4 and potentially EphB2 to stimulate osteoblast maturation and function (Allan et al, 2008).
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