Post-Transcriptional Regulation of Osteoblastic Platelet-Derived Growth Factor Receptor-Alpha Expression by Co-Cultured Primary Endothelial Cells

作者：Finkenzeller Guenter^*; Mehlhorn Alexander T; Schmal Hagen; Stark G Bjoern

来源：Cells Tissues Organs, 2010, 192(1): 28-38.

DOI：10.1159/000276590

• Endothelial cell
• Osteoblast
• Co-culture
• Mesenchymal stem cell
• Platelet-derived growth factor receptor expression

Platelet-derived growth factor receptor (PDGFR) signaling plays an important role in osteoblast function. Inhibition of PDGFR activity leads to a suppression of osteoblast proliferation, whereas mineralized matrix production is enhanced. In previous experiments, we showed that co-cultivation of human primary endothelial cells and human primary osteoblasts (hOBs) leads to a cell contact-dependent downregulation of PDGFR-alpha expression in the osteoblasts. In this study, we investigated this effect in more detail, revealing that human umbilical vein endothelial cell (HUVEC)-mediated PDGFR-alpha downregulation is dependent on time and cell number. This effect was specific to endothelial cells and was not observed when hOBs were co-cultured with human primary chondrocytes or fibroblasts. Likewise, HUVEC-mediated suppression of PDGFR-alpha expression was only seen in hOBs and mesenchymal stem cells but not in immortalized osteoblastic cell lines. Functional inhibition of gap junctional communication between HUVECs and hOBs by 18 alpha-glycyrrhetinic acid had no effect on HUVEC-mediated PDGFR-alpha downregulation, whereas inhibition of p38 mitogen-activated protein kinase (MAPK) prevented the HUVEC-mediated reduction in osteoblastic PDGFR-alpha expression. To delineate the molecular mechanism underlying the PDGFR-alpha down-regulation, we examined the effect of HUVEC co-cultivation on osteoblastic PDGFR-alpha promoter activity as well as mRNA stability. Co-cultivation of HUVECs with hOBs significantly shortened the half-life of osteoblastic PDGFR-alpha mRNA, but did not decrease its promoter activity. In summary, our data show that PDGFR-alpha is downregulated in hOBs by co-cultivation with human primary endothelial cells through a p38 MAPK-dependent post-transcriptional mechanism.

• 出版日期2010