Deletion of Fgfr1 in osteoblasts enhances mobilization of EPCs into peripheral blood in a mouse endotoxemia model.

Endothelial progenitor cells (EPCs) contribute to neovascularization and vascular repair, and may exert a beneficial effect on the clinical outcome of sepsis. Osteoblasts act as a component of "niche" in bone marrow, which provides a nest for stem/progenitor cells and are involved in the formation and maintenance of stem/progenitor cells. Fibroblast growth factor receptor 1 (FGFR1) can regulate osteoblast activity and influence bone mass. So we explored the role of FGFR1 in EPC mobilization. Male mice with osteoblast-specific knockout of Fgfr1 (Fgfr1(fl/fl);OC-Cre) and its wild-type littermates (Fgfr1(fl/fl) ) were used in this study. Mice intraperitoneally injected with lipopolysaccharide (LPS) were used to measure the number of circulating EPCs in peripheral blood and serum stromal cell-derived factor 1α (SDF-1α). The circulating EPC number and the serum level of SDF-1α were significantly higher in Fgfr1(fl/fl);OC-Cre mice than those in Fgfr1(fl/fl) mice after LPS injection. In cell culture system, SDF-1α level was also significantly higher in Fgfr1(fl/fl);OC-Cre osteoblasts compared with that in Fgfr1(fl/fl) osteoblasts after LPS treatment. TRAP staining showed that there was no significant difference between the osteoclast activity of septic Fgfr1(fl/fl) and Fgfr1(fl/fl);OC-Cre mice. This study suggests that targeted deletion of Fgfr1 in osteoblasts enhances mobilization of EPCs into peripheral blood through up-regulating SDF-1α secretion from osteoblasts.

Pubmed ID: 25285038 RIS Download