INTERLEUKIN-1 AND TUMOR NECROSIS FACTOR STIMULATE THE FORMATION OF HUMAN OSTEOCLASTLIKE CELLS-INVITRO
INTERLEUKIN-1 AND TUMOR NECROSIS FACTOR STIMULATE THE FORMATION OF HUMAN OSTEOCLASTLIKE CELLS-INVITRO
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DOI：
10.1002/jbmr.5650040116
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发表时间：
1989-02-01
影响因子：
6.2
通讯作者：
ROODMAN, GD
中科院分区：
文献类型：
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作者：
PFEILSCHIFTER, J;CHENU, C;ROODMAN, GD
白细胞介素-1（IL-1）α和β和肿瘤坏死因子（TNF）α。和β是体外和体内骨吸收的有效刺激剂。然而，这种骨吸收增加的机制尚未明确定义。骨吸收增加可由单个破骨细胞的活性增加、破骨细胞数量增加或两者引起。因此，我们使用了一个长期的人骨髓培养系统，形成具有破骨细胞特性的多核细胞（MNC），以检查IL-1和TNF对破骨细胞形成的影响。人重组IL-1 α。和IL-1 β。和人重组TNF-α。和TNF-β。从4- 60倍IL-1 α刺激MNC形成，IL-1 β，TNF-α，和TNF-β。在非常低的浓度下显著增加MNC的形成：2.5 × 10 - 6。IL-1 α为10-13 M。和IL-1 β，TBF-α为10-11 M，TNF-β为10-10 μ M。此外，这些细胞因子在1，25-二羟维生素D3 [1，25-（OH）2D 3]存在下增强MNC形成，1，25-（OH）2D 3是一种通过刺激单核前体细胞融合来刺激MNC形成的强效成骨因子。同时加入IL-1和TNF的文化导致了协同刺激的MNC形成。这些结果表明：（1）IL-1和TNF部分通过增加破骨细胞形成刺激骨吸收，和（2）极低浓度的这些因子可以在不存在其他因子（如1，25-（OH）2D 3）的情况下协同增加破骨细胞形成。这些数据表明，细胞因子之间的协同相互作用在维持正常和病理状态下的骨细胞活性中起重要作用。
Interleukin-1 (IL-1) .alpha. and .beta. and tumor necrosis factor (TNF) .alpha. and .beta. are potent stimulators of bone resorption in vitro and in vivo. However, the mechanisms underlying this increased bone resorption have not been clearly defined. Increased bone resorption can result from increased activity of individual osteoclasts, increased numbers of osteoclasts, or both. Therefore, we have used a long-term human marrow culture system that forms multinucleated cells (MNC) with the characteristics of osteoclasts to examine the effects of IL-1 and TNF on osteoclast formation. Human recombinant IL-1.alpha. and IL-1.beta. and human recombinant TNF-.alpha. and TNF-.beta. stimulated MNC formation from 4- to 60-fold IL-1.alpha., IL-1.beta., TNF-.alpha., and TNF-.beta. significantly increased MNC formation at very low concentrations: 2.5 .times. 10-13 M for IL-1.alpha. and IL-1.beta., 10-11 M for TBF-.alpha., and 10-10 M for TNF-.beta.. In addition, these cytokines enhanced MNC formation in the presence of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], a potent osteotropic factor that stimulates MNC formation by stimulating fusion of mononuclear precursor cells. Simultaneous addition of IL-1 and TNF to the cultures resulted in a synergistic stimulation of MNC formation. These results suggest that: (1) IL-1 and TNF stimulate bone resorption in part by increasing osteoclast formation and (2) an extremely low concentration of these factors can synergistically increase osteoclast formation in the absence of other factors, such as 1,25-(OH)2D3. These data suggest that synergistic interactions among cytokines play an important role in maintaining bone cell activity in normal and pathologic states.