TNF-related activation-induced cytokine(TRANCE), a member of the TNF family, is highly expressed on osteoblasts and plays a key role in the control of bone development. Because angiogenesis is the crucial first step in the processes of proper bone for...
TNF-related activation-induced cytokine(TRANCE), a member of the TNF family, is highly expressed on osteoblasts and plays a key role in the control of bone development. Because angiogenesis is the crucial first step in the processes of proper bone formation, we tested the hypothesis that TRANCE is able to induce the growth of new blood vessels. TRANCE evoked a time- and dose-dependent activation of the mitogen-activated protein kinases ERK1/2, AKT and NF-B in human umbilical vein endothelial cells(HUVECs). TRANCE stimulated in vitro DNA synthesis, chemotactic motility, and capillary-like tube formation of HUVECs. Both Matrigel plug assay in mice and chick chorioallantoic membrane(CAM) assay revealed that TRANCE potently induced neovascularization in vivo. These results indicate that TRANCE, presumably via activation of the endothelial TRANCE receptor, stimulates various angiogenic signaling pathways in endothelial cells. Thus, TRANCE may act as an important modulator of angiogenesis under the physiological and pathological conditions.