Co-culture with endothelial progenitor cells promotes survival, migration, and differentiation of osteoclast precursors

► Co-culture of RAW 264.7 monocyte cells with endothelial progenitor cells (EPCs). ► EPCs enhanced survival, migration, and differentiation of RAW 264.7 cells. ► VEGF, SDF-1, and TGF-β1 from EPCs are involved in the regulation of RAW 264.7 cells. ► Presence of EPCs increased expression of VEGFR-2, CXCR4, Smad2/3, Akt, and MAPKs. In this study, we report the effect of endothelial progenitor cells (EPCs) on the biological behavior of osteoclast precursors in vitro by establishing an indirect co-culture system of mice EPCs and RAW 264.7 monocyte cells. Results show that the survival, migration, and differentiation of osteoclast precursors were greatly enhanced when co-cultured with EPCs. These phenotypic changes coincide with the upregulation of multiple genes affected cell behavior, including phospho-VEGFR-2, CXCR4, phospho-Smad2/3, phospho-Akt, phospho-ERK1, and phospho-p38 MAPK. The results collectively suggest that EPCs could modulate the survival, migration, and differentiation potential of osteoclast precursors, thus providing new insights in understanding of correlation between angiogenesis and bone homeostasis.