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Researchers are in constant search for the ideal implant surface condition in an attempt to improve osseointegration and to increase bone-to-implant contact. Although various techniques such as physicochemical and morphologic modification, have been proposed, they are still incapable of ensuring predictable results and guaranteed success. In recent years, investigators have also attempted to improve bone formation around implants via using biochemical modification. Various kinds of biomolecules have been introduced to endow the titanium surfaces bioactivities because of their certain bone-growth promoting capabilities. A review of the research progress is given in this paper concerning the biochemical modification of the implant surface.

The EphB4 receptor and ephrin B2 ligand were recently reported to influence the coupling between osteoclasts and osteoblasts in bone biology, but their downstream signaling pathways remain unclear. This study focuses on the preliminary identification of downstream PDZ-domain proteins involved in EphB4/ephrin B2 reverse signaling in osteoclasts. Similarly to primary osteoclast precursors isolated from the bone, we observed that the RAW264.7 cell line, a mouse monocyte/macrophage cell line that is used in conventional assays for osteoclast function, expressed ephrin B2 during RANKL-induced osteoclast differentiation, and that preclustered EphB4 inhibited this osteoclast differentiation. The results demonstrate that RAW264.7 cells provide a good model for further research of EphB4/ephrin B2 signaling in osteoclasts. Immunofluorescence staining and Western blot analysis revealed that all of the eight PDZ-domain proteins previously reported to interact with ephrin B ligands were expressed in the differentiated RAW264.7 osteoclasts. However, in a co-immunoprecipitation assay, only Dishevelled 2 (Dvl2) among eight PDZ-domain proteins tested co-precipitated with ephrin B2 and vice versa, suggesting an endogenous interaction between Dvl2 and ephrin B2 in RANKL-induced osteoclasts. Furthermore, preclustered EphB4 reduced the expression level of Dvl2. Collectively, our results indicate that Dvl2 could be the potential PDZ-domain protein that acts downstream of ephrin B2 in RANKL-induced osteoclast differentiation of RAW264.7 cells, providing a potential novel therapeutic target for bone diseases.