Production of interleukin-11 in bone-derived endothelial cells and its role in the formation of osteolytic bone metastasis
Production of interleukin-11 in bone-derived endothelial cells and its role in the formation of osteolytic bone metastasis
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DOI：
10.1038/sj.onc.1201581
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发表时间：
1998-02-12
期刊：
影响因子：
8
通讯作者：
Tsuruo, T
中科院分区：
文献类型：
--
作者：
Zhang, Y;Fujita, N;Tsuruo, T
骨微环境中细胞的相互作用在骨重塑中发挥着重要作用，成骨细胞通过产生调节破骨细胞增殖和分化的可溶性因子以及通过细胞与细胞的相互作用参与骨重塑。组织学研究表明内皮细胞也与一些溶骨性骨疾病相关，然而，目前尚不清楚内皮细胞如何促进骨吸收，我们建立了骨源性内皮细胞（BDEC）来研究其在骨重塑中的作用，所建立的BDEC通过分泌可溶性骨促进小鼠新生儿颅盖器官培养系统中的骨吸收 当受到几种炎症细胞因子刺激时，会产生吸收诱导因子。这种骨吸收诱导因子被鉴定为白细胞介素-II (IL-11)。已知IL-11通过促进破骨细胞生成和抑制成骨细胞的活性来增强骨吸收，人黑色素瘤A375M细胞的条件培养基也促进BDEC中IL-11的产生，由于A375M细胞在体内形成溶骨性骨转移，BDEC可能通过产生IL-11参与病理性骨溶解。 IL-11，这些结果表明骨内皮细胞在生理和病理条件下通过分泌IL-11在促进骨吸收中发挥重要作用。
The interactions of the cells in the bone microenvironment play important roles in bone remodeling, Osteoblasts are involved in the bone remodeling through the production of soluble factors that regulate proliferation and differentiation of osteoclasts and through cell-cell interactions. Histological studies have suggested that endothelial cells are also associated with some osteolytic bone diseases, However, it is still unclear how endothelial cells contribute to bone resorption, We established bone-derived endothelial cells (BDECs) to study their roles in bone remodeling, The established BDECs promoted bone resorption in a murine neonatal calvaria organ culture system by secreting a soluble bone resorption-inducing factor(s) when stimulated by several inflammatory cytokines. This bone resorption-inducing factor was identified as interleukin-ll (IL-11). IL-11 is known to enhance bone resorption by promoting osteoclastogenesis and by suppressing the activity of osteoblasts, The production of IL-11 in BDECs was also promoted by conditioned medium of human melanoma A375M cells, Because A375M cells formed osteolytic bone metastasis in vivo, BDECs might be involved in pathological osteolysis by producing IL-11, These results suggest that endothelial cells in bone play important roles in the promotion of bone resorption by secreting IL-11 in physiological and pathological conditions.