INTERLEUKIN-11 - A NEW CYTOKINE CRITICAL FOR OSTEOCLAST DEVELOPMENT
INTERLEUKIN-11 - A NEW CYTOKINE CRITICAL FOR OSTEOCLAST DEVELOPMENT
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DOI：
10.1172/jci117130
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发表时间：
1994-04-01
影响因子：
15.9
通讯作者：
MANOLAGAS, SC
中科院分区：
文献类型：
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作者：
GIRASOLE, G;PASSERI, G;MANOLAGAS, SC
骨髓基质细胞通过产生能够促进造血祖细胞增殖和分化的细胞因子来控制破骨细胞的发育。此外，骨髓中细胞因子IL-6的生产失调介导了雌激素缺失后破骨细胞生成的增加。然而，IL-6在雌激素充满状态下不影响破骨细胞的形成，这表明在生理环境下，其他细胞因子可能负责破骨细胞的发育。我们在这里报道了IL-11，一种由骨髓基质细胞产生的新发现的细胞因子，诱导破骨细胞的形成，在小鼠骨髓和颅骨细胞共培养中表现出异常高的倍性。在IL-11存在下形成的破骨细胞能够骨吸收，这可以通过骨吸收坑的形成以及预标记小鼠颅骨中Ca-45的释放来证明。此外，中和IL-11的抗体可抑制1,25-二羟基维生素D-3、甲状旁腺激素、白细胞介素-1或肿瘤坏死因子诱导的破骨细胞发育；而IL-1或TNF抑制剂对il -11刺激的破骨细胞形成没有影响。吲哚美辛可阻断IL-11对破骨细胞发育的影响；然而，更重要的是，它们与骨髓供者的雌激素水平无关。
Stromal cells of the bone marrow control the development of osteoclasts through the production of cytokines capable of promoting the proliferation and differentiation of hematopoietic progenitors. Moreover, the deregulated production of the cytokine IL-6 in the bone marrow mediates an increase in osteoclastogenesis after estrogen loss. IL-6, however, does not influence osteoclastogenesis in the estrogen-replete state, suggesting that other cytokines might be responsible for osteoclast development under physiologic circumstances. We report here that IL-11, a newly discovered cytokine that is produced by marrow stromal cells, induced the formation of osteoclasts exhibiting an unusually high degree of ploidy in cocultures of murine bone marrow and calvarial cells. Osteoclasts formed in the presence of IL-11 were capable of bone resorption, as evidenced by the formation of resorption pits, as well as the release of Ca-45 from prelabeled murine calvaria. Further, an antibody neutralizing IL-11 suppressed osteoclast development induced by either 1,25-dihgdroxyvitamin D-3, parathyroid hormone, interleukin-1, or tumor necrosis factor; whereas inhibitors of IL-1 or TNF had no effect on IL-11-stimulated osteoclast formation. The effects of IL-11 on osteoclast development were blocked by indomethacin; more important, however, they were independent of the estrogen status of the marrow donors.