Int J Biol Sci 2014; 10(9):1064-1071. doi:10.7150/ijbs.8415
Deletion of Fgfr1 in Osteoblasts Enhances Mobilization of EPCs into Peripheral Blood in a Mouse Endotoxemia Model
1. Department of Rehabilitation Medicine, Center of Bone Metabolism and Repair, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China;
2. The Department of Intensive Care, Chongqing Zhongshan Hospital, Chongqing 400013, China.
*These authors contributed equally to this work.
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 (Fgfr1fl/fl;OC-Cre) and its wild-type littermates (Fgfr1fl/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 Fgfr1fl/fl;OC-Cre mice than those in Fgfr1fl/fl mice after LPS injection. In cell culture system, SDF-1α level was also significantly higher in Fgfr1fl/fl;OC-Cre osteoblasts compared with that in Fgfr1fl/fl osteoblasts after LPS treatment. TRAP staining showed that there was no significant difference between the osteoclast activity of septic Fgfr1fl/fl and Fgfr1fl/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.
Keywords: FGFR1, Endotoxemia, LPS, EPCs, Osteoblast, SDF-1α.
Zhang Y, Su N, Luo F, Wen X, Tang Y, Yang J, Chen S, Jiang W, Du X, Chen L. Deletion of Fgfr1 in Osteoblasts Enhances Mobilization of EPCs into Peripheral Blood in a Mouse Endotoxemia Model. Int J Biol Sci 2014; 10(9):1064-1071. doi:10.7150/ijbs.8415. Available from http://www.ijbs.com/v10p1064.htm