Mode of action of interleukin-6 on mature osteoclasts. Novel interactions with extracellular Ca2+ sensing in the regulation of osteoclastic bone resorption.
Mode of action of interleukin-6 on mature osteoclasts. Novel interactions with extracellular Ca2+ sensing in the regulation of osteoclastic bone resorption.
复制标题
DOI：
10.1083/jcb.142.5.1347
复制
发表时间：
1998-09-07
期刊：
影响因子：
--
通讯作者：
Zaidi M
中科院分区：
文献类型：
--
作者：
Adebanjo OA;Moonga BS;Yamate T;Sun L;Minkin C;Abe E;Zaidi M
我们描述了一个生理上重要的机制，通过白细胞介素-6 （IL-6）和上升的环境Ca2+相互作用来调节破骨细胞骨吸收。与抗IL-6受体抗体孵育的非通透性破骨细胞的voxel共聚焦显微镜显示强烈的，严格的外周质膜荧光。原位逆转录酶PCR组织化学证实IL-6受体在单个破骨细胞中的表达。IL-6 （5 ng/l ~ 10 μg/l）逆转了高细胞外Ca2+ (15 mM)诱导的破骨细胞骨吸收抑制，而IL-11（10和100 μg/l）则没有逆转作用。过量的可溶性IL-6受体（500 μg/l）可消除IL-6的作用。此外，IL-6 （5 pg/l ~ 10 μg/l）抑制高Ca2+或Ni2+触发的胞质Ca2+信号。在单独的实验中，在10 mM Ca2+中或骨上培养的破骨细胞比在1.25 mM Ca2+中培养的破骨细胞释放更多的IL-6。此外，IL-6 mRNA组织染色在10或20 mM Ca2+中的破骨细胞中比在1.25 mM Ca2+中的细胞更强烈。同样，在5或10 mM Ca2+中培养的破骨细胞中，IL-6受体mRNA组织染色增加。因此，虽然高Ca2+增强了IL-6的分泌，但释放的IL-6减弱了Ca2+的感知并逆转了Ca2+对再吸收的抑制。这种自分泌-旁分泌循环可能在面对吸收过程中局部产生的抑制性Ca2+水平时维持破骨活性。
We describe a physiologically significant mechanism through which interleukin-6 (IL-6) and a rising ambient Ca2+ interact to regulate osteoclastic bone resorption. VOXEL-based confocal microscopy of nonpermeabilized osteoclasts incubated with anti– IL-6 receptor antibodies revealed intense, strictly peripheral plasma membrane fluorescence. IL-6 receptor expression in single osteoclasts was confirmed by in situ reverse transcriptase PCR histochemistry. IL-6 (5 ng/l to 10 μg/l), but not IL-11 (10 and 100 μg/l), reversed the inhibition of osteoclastic bone resorption induced by high extracellular Ca2+ (15 mM). The IL-6 effect was abrogated by excess soluble IL-6 receptor (500 μg/l). Additionally, IL-6 (5 pg/l to 10 μg/l) inhibited cytosolic Ca2+ signals triggered by high Ca2+ or Ni2+. In separate experiments, osteoclasts incubated in 10 mM Ca2+ or on bone released more IL-6 than those in 1.25 mM Ca2+. Furthermore, IL-6 mRNA histostaining was more intense in osteoclasts in 10 or 20 mM Ca2+ than cells in 1.25 mM Ca2+. Similarly, IL-6 receptor mRNA histostaining was increased in osteoclasts incubated in 5 or 10 mM Ca2+. Thus, while high Ca2+ enhances IL-6 secretion, the released IL-6 attenuates Ca2+ sensing and reverses inhibition of resorption by Ca2+. Such an autocrine–paracrine loop may sustain osteoclastic activity in the face of an inhibitory Ca2+ level generated locally during resorption.
登录
查看更多内容
影响因子：
11.4
作者：
HILTON, DJ;HILTON, AA;WILLSON, TA
通讯作者：
WILLSON, TA
影响因子：
4.8
作者：
Bellido, T;Borba, VZC;Manolagas, SC
通讯作者：
Manolagas, SC
影响因子：
56.9
作者：
JILKA, RL;HANGOC, G;MANOLAGAS, SC
通讯作者：
MANOLAGAS, SC
影响因子：
5.3
作者：
SHENG, M;DOUGAN, ST;GREENBERG, ME
通讯作者：
GREENBERG, ME
影响因子：
2.6
作者：
BOYDE, A;ALI, NN;JONES, SJ
通讯作者：
JONES, SJ