Dr. Christian J. Veillette

Endothelin-1 (ET-1), a peptide produced by vascular endothelial cells (VECs), is implicated in the signaling between VECs, osteoblasts, and osteoclasts in bone development, remodeling and repair. Vascular endothelial growth factor (VEGF) also plays an important signaling role in these intercellular interactions and has been implicated in osteoblast differentiation, osteoclast formation and angiogenesis. Our objectives were to determine the effects of ET-1 on the mRNA expression and protein production of VEGF isoforms during osteoprogenitor proliferation and differentiation. Three VEGF mRNA isoforms were identified in osteoblastic cell populations from fetal rat calvarial (FRC) cells, corresponding to VEGF120, 164 and 188 isoforms. Predominate isoforms, VEGF 120 and 164, were expressed during the early proliferative phase (day 4), decreased during the late proliferative and early maturation phase (day 7-10), and increased during the late maturation/ mineralization phase (day 10-18). ET-1 down-regulated VEGF expression and sustained the down-regulation over time in long-term cultures. Furthermore, ET-1 inhibited VEGF mRNA expression by up to 2 fold after incubation for 3 hours in 7- and 14- day FRC cells. VEGF-A protein secretion was inhibited by ET-1in a dose-dependent manner; with a maximal effect at 10-7 M. ET-1 (10-8 M) inhibited VEGF protein secretion after 24 hours by 5.8 fold and 2.8 fold in 7- and 14- day FRC cells, respectively. Our results identify ET-1 as the first peptide inhibitor of VEGF synthesis in osteoblastic cells and suggests that ET-1 may have a unique function in the paracrine control of VEGF dependent processes, such as angiogenesis and osteoclast formation/activity, via inhibition of osteoblast-derived VEGF during bone development and remodeling. This novel feedback mechanism may be important in the temporal and spatial coupling of angiogenesis to bone formation and resorption and is of potential significance for understanding normal bone physiology and pathological mechanism

Development and implementation of a Web based surgical logbook and residency management system
Usage of Internet resources in post graduate medical education