Interleukin-1 alpha induces cyclooxygenase-2 expression in bone-derived endothelial cells

Histological studies have suggested that vascular endothelial cells in bone are members of a complex network that regulates bone development and remod eling by producing soluble factors or by mediating cell-cell adhesion. To c larify the role of bone-derived endothelial cell lines (BDECs) in bone remo deling, we established several clones of BDECs from the femurs of BALB/c mi ce after transformation with the SV40 virus. Then we examined the response of these clones to interleukin-1 alpha (IL-1 alpha). IL-1 alpha is known to induce bone resorption in part by increasing the expression of cyclooxygen ase-2 (COX-2) that is associated wi th the production of PGE(2) in osteobla st-lineage cells. Treating the primary and established BDECs with IL-1 alph a induced COX-2 mRNA expression. A transcriptional activation assay reveale d that the treatment with IL-1 alpha increased COX-2 promoter activity in a dose-dependent manner, and IL-1 alpha promoted COX-2 protein expression in BDECs. Treatment with IL-1 alpha promoted PGE(2) production from BDECs in a dose-dependent manner. These results indicate that IL-1 alpha stimulates PGE(2) synthesis largely by inducing BDECs to express COX-2. Because PGE(2) stimulates hone resorption, these vascular endothelial cells, as well as o steoblast cells, play important roles in bone remodeling. (C) 1999 Wiley-Li ss, Inc.