The Role of MAP Kinase in The Signal Transduction Pathways Activated by Mechanical Stress in Mesenchymal Cells.

MAP 激酶在间充质细胞机械应力激活的信号转导途径中的作用。

• 批准号: 09672094
• 负责人: MORIYAMA Keiji
• 金额: $ 2.05万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09672094/
• 关键词: mechanical stress; IL-6; soluble IL-6receptor; gp130; MAP kinase; JAK-STAT; osteoblast; メカニカメストレス; 歯根膜細胞; 力学的刺激; チロシンリン酸化; src

Studies on interleukin-6 (IL-6) in bone metabolism in response to mechanical stress have been accumulating. However, its effects on osteoblasts are still unclear because the results are conflicting depending on the study models employed. We reasoned that these conflicting data are due to variable expression levels of membrane-bound IL-6 receptors (IL-6Rs). In the present study, we found that IL-6 in combination with soluble IL-6R (sIL-6R) consistently caused a marked elevation of alkaline phosphatase and a decrease in proliferation in the human osteoblastic cell line MG-63, which expressed no detectable membrane-bound IL-6R and failed to respond to IL-6. These effects of IL-6/sIL-6R were blocked by neutralizing antibodies to the IL-6 signal transducer gp 130, suggesting an involvement of IL-6 signaling in the elicitation of the effects of IL-6/sIL6R.Upon stimulation with IL-6/sIL-6R, the gp 130, cytoplasmic Janus kinases JAK1 and JAK2 were tyrosine phosphorylated. Moreover, signal transducers and activators of transcription STAT1 and STAT3 were also tyrosine phosphorylated, translocated to the nucleus, and bound to the putative STAT-binding DNA elements. In addition, mitogen-activated protein (MAP) kinase was also activated in response to IL-6/sIL-6R.These data demonstrate that sIL-SR may enhance the responsiveness of MG-63 cells to IL-6. Thus, IL-6 in collaboration with sIL-6R may modulate differentiation and proliferation of osteoblastic cells, presumably by activating two distinct signaling pathways of JAK-STAT and MAP kinase.

关于白细胞介素 6 (IL-6) 在骨代谢中响应机械应力的研究不断积累。然而，它对成骨细胞的影响仍不清楚，因为根据所采用的研究模型，结果是相互矛盾的。我们推断这些相互矛盾的数据是由于膜结合 IL-6 受体 (IL-6R) 的表达水平不同所致。在本研究中，我们发现 IL-6 与可溶性 IL-6R (sIL-6R) 组合一致导致人成骨细胞系 MG-63 中碱性磷酸酶显着升高和增殖减少，该细胞系未检测到表达膜结合 IL-6R，对 IL-6 没有反应。 IL-6/sIL-6R 的这些作用被 IL-6 信号转导器 gp 130 的中和抗体阻断，表明 IL-6 信号传导参与了 IL-6/sIL6R 作用的引发。 -6/sIL-6R、gp 130、细胞质 Janus 激酶 JAK1 和 JAK2 被酪氨酸磷酸化。此外，转录STAT1和STAT3的信号转导子和激活子也被酪氨酸磷酸化，转移到细胞核，并与假定的STAT结合DNA元件结合。此外，丝裂原激活蛋白（MAP）激酶也响应IL-6/sIL-6R而被激活。这些数据表明sIL-SR可以增强MG-63细胞对IL-6的反应性。因此，IL-6 与 sIL-6R 协同作用可能通过激活 JAK-STAT 和 MAP 激酶这两个不同的信号通路来调节成骨细胞的分化和增殖。

项目成果

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