Inflammatory cytokines (IL-1α, TNF-α) and LPS modulate the Ca2+ signaling pathway in osteoblasts
Inflammatory cytokines (IL-1α, TNF-α) and LPS modulate the Ca2+ signaling pathway in osteoblasts
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DOI：
10.1152/ajpcell.1998.274.6.c1686
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发表时间：
1998-06-01
影响因子：
5.5
通讯作者：
Green, J
中科院分区：
文献类型：
--
作者：
Tam, VK;Schotland, S;Green, J
骨中局部衍生的生长因子和细胞因子在骨重塑（即骨形成和骨吸收过程）的调节中起着至关重要的作用。我们研究了白细胞介素 (IL)-1 α、肿瘤坏死因子 (TNF)-α 和大肠杆菌脂多糖 (LPS) 对成骨细胞系 UMR-106 和新生大鼠颅骨来源的成骨细胞培养物中激素激活的 Ca2+ 信息系统的影响，在两种细胞制剂中，IL-1 α、TNF-α 和 LPS 不会改变基础细胞内 Ca2+ 浓度([Ca2+](i)) 但减弱的 Ca2+ 瞬变是由甲状旁腺激素 (PTB) 和 PGE(2) 以剂量 (1-100 ng/ml) 和时间 (8-24 h) 依赖性方式演变的。细胞因子调节激素诱导的 Ca2+ 流入（通过使用 Mn2+ 作为 Ca2+ 的替代物估计）以及细胞内储备的 Ca2+ 动员。后者与激素诱导的肌醇 1,4,5-三磷酸的抑制产生有关。细胞因子对 [Ca2+](i) 的影响被酪氨酸激酶抑制剂除草霉素 A (50 ng/ml) 消除。然而，细胞因子的作用与一氧化氮 (NO) 的产生无关，因为 NO 供体（硝普钠）以及可渗透的 cGMP 类似物会增强而不是减弱成骨细胞中激素诱导的 Ca2+ 瞬变。鉴于细胞因子对成骨细胞中 NO 产生的刺激作用，细胞因子和 NO 对 Ca2+ 信号通路的不同作用可能是调节促钙激素对骨代谢作用的自分泌/旁分泌机制。
Locally derived growth factors and cytokines in bone play a crucial role in the regulation of bone remodeling, i.e., bone formation and bone resorption processes. We studied the effect of interleukin (IL)-1 alpha, tumor necrosis factor (TNF)-alpha, and Escherichia coli lipopolysaccharide (LPS) on the hormone-activated Ca2+ message system in the osteoblastic cell line UMR-106 and in osteoblastic cultures derived from neonatal rat calvariae, in both cell preparations, IL-1 alpha, TNF-alpha, and LPS did not alter basal intracellular Ca2+ concentration ([Ca2+](i)) but attenuated Ca2+ transients evolved by parathyroid hormone (PTB) and PGE(2) in a dose(1-100 ng/ml)-and time(8-24 h)dependent fashion. The cytokines modulated hormonally induced Ca2+ influx (estimated by using Mn2+ as a surrogate for Ca2+) as well as Ca2+ mobilization from intracellular stores. The latter was linked to suppressed production of hormonally induced inositol 1,4,5-trisphosphate. The effect of cytokines on [Ca2+](i) was abolished by the tyrosine kinase inhibitor herbimycin A (50 ng/ml). The cytokine's effect was, however, independent of nitric oxide (NO) production, since NO donors (sodium nitroprusside) as well as permeable cGMP analogs augment, rather than attenuate, hormonally induced Ca2+ transients in osteoblasts. Given the stimulatory role of cytokines on NO production in osteoblasts, the disparate effects of cytokines and NO on the Ca2+ signaling pathway may serve an autocrine/paracrine mechanism for modulating the effect of calciotropic hormones on bone metabolism.