Endothelin modulates osteopontin and osteocalcin messenger ribonucleic acid expression in rat osteoblastic osteosarcoma cells.

Endothelins (ETs) are vasoconstrictive peptides produced mainly by endothelial cells. The ET receptors are expressed in many types of cells including osteoblast-like cells. The purpose of this study was to examine the effects of endothelin on the expression of osteoblastic phenotype-related genes. We found that endothelin-1 (ET-1) enhanced approximately two-fold the mRNA expression of both osteopontin and osteocalcin genes in rat osteoblastic osteosarcoma ROS17/2.8 cells. These effects were dose-dependent, peaking at 10(-7) M. The ET-1 enhancement of the abundance of osteopontin and osteocalcin mRNAs was time-dependent, with a maximal effect at 24 h. ET-1 modulation of the expression of the two phenotype-related gene products of osteoblasts suggests that endothelin is one of the cytokines which modulate osteoblastic functions and that this molecule may play a role in the regulation of bone metabolism.