Interleukin-1 alpha induced 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 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-1alpha (IL-1alpha). IL-1alpha 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-1alpha induced COX-2 mRNA expression. A transcriptional activation assay revealed that the treatment with IL-1alpha increased COX-2 promoter activity in a dose-dependent manner, and IL-1alpha promoted COX-2 protein expression in BDECs. Treatment with IL-1alpha promoted PGE2 production from BDECs in a dose-dependent manner. These results indicate that IL-1alpha 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.
Nakagawa
T
T
Institute of Molecular and Cellular Biosciences, Department of Orthopedic Surgery, University of Tokyo, Japan.
Fujita
N
N
Oh-Hara
T
T
Kurokawa
T
T
Nakamura
K
K
Tsuruo
T
T
D000818:Animals; D016723:Bone Remodeling / Q000187:drug effects*; D002460:Cell Line; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects*; D005269:Femur / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007375:Interleukin-1 / Q000494:pharmacology*; D007527:Isoenzymes / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000187:drug effects; D014162:Transfection; D014170:Transformation, Genetic
D007375:Interleukin-1; D007527:Isoenzymes; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone