Interleukin‐1α induces cyclooxygenase‐2 expression in bone‐derived endothelial cells

Abstract

Histological studies have suggested that vascular endothelial cells in bone are members of a complex network that regulates bone development and remodeling by producing soluble factors or by mediating cell-cell adhesion. To clarify the role of bone-derived endothelial cell lines (BDECs) in bone remodeling, we established several clones of BDECs from the femurs of BALB/c mice after transformation with the SV40 virus. Then we examined the response of these clones to interleukin-1α (IL-1α). IL-1α is known to induce bone resorption in part by increasing the expression of cyclooxygenase-2 (COX-2) that is associated with the production of PGE2 in osteoblast-lineage cells. Treating the primary and established BDECs with IL-1α induced COX-2 mRNA expression. A transcriptional activation assay revealed that the treatment with IL-1α increased COX-2 promoter activity in a dose-dependent manner, and IL-1α promoted COX-2 protein expression in BDECs. Treatment with IL-1α promoted PGE2 production from BDECs in a dose-dependent manner. These results indicate that IL-1α stimulates PGE2 synthesis largely by inducing BDECs to express COX-2. Because PGE2 stimulates bone resorption, these vascular endothelial cells, as well as osteoblast cells, play important roles in bone remodeling. J. Cell. Physiol. 179:226–232, 1999. © 1999 Wiley-Liss, Inc.