High glucose and palmitate increases bone morphogenic protein 4 expression in human endothelial cells

Here, we investigated whether hyperglycemia and/or free fatty acids (palmitate, PAL) aff ect the expression level of bone morphogenic protein 4 (BMP4), a proatherogenic marker, in endothelial cells and the potential role of BMP4 in diabetic vascular complications. To measure BMP4 expression, human umbilical vein endothelial cells (HUVECs) were exposed to high glucose concentrations and/or PAL for 24 or 72 h, and the effects of these treatments on the expression levels of adhesion molecules and reactive oxygen species (ROS) were examined. BMP4 loss-of-function status was achieved via transfection of a BMP4-specific siRNA. High glucose levels increased BMP4 expression in HUVECs in a dose-dependent manner. PAL potentiated such expression. The levels of adhesion molecules and ROS production increased upon treatment with high glucose and/or PAL, but this eff ect was negated when BMP4 was knocked down via siRNA. Signaling of BMP4, a proinflammatory and pro-atherogenic cytokine marker, was increased by hyperglycemia and PAL. BMP4 induced the expression of infl ammatory adhesion molecules and ROS production. Our work suggests that BMP4 plays a role in atherogenesis induced by high glucose levels and/or PAL.

Gene therapy of firearm femur defect by using BMP-4/TGF-β1 in rabbits / 中华创伤杂志

Objective To observe effects of BMP-4 gene combined with TGF-β1 in repairing rabbit femur defect resulted from firearm wound. Methods The femur defect was made with firearm steel ball. Plasmid encoded BMP-4 gene identified in vitro and TGF-β1 were injected into the tissue of upper, lower and central parts of the defects at the second week after wound. The mRNA and protein expressions of BMP-4 in vivo were detected by real time-polymerase chain reaction (RT-PCR) and Western blot. Activity of alkaline phosphatase (ALP) and calcium content were measured for evaluating osteogenetic ability. The process and quality of osteogenesis were determined by pathological and X-ray examinations. Results mRNA and protein of BMP-4 could continually express for six weeks in vivo after injection. Activity of ALP in the experimental group was increased to ( 13.17 ±0.51 ) U/100 ml at the 8th week, which was significantly higher than (8.77 ± 0.44) U/100 ml in the control group, indicating that osteogenetic ability was markedly enhanced, which accorded with determination of calcium content. Pathological observation and X-ray proved prominent improvement of osteogenesis, with a shorter time and better quality, in the experimental group. Conclusion BMP-4/TGF-β1 can promote repair of firearm femur defect.