Role of Cytokines Signaling in Osteoblastic Differentiation

细胞因子信号传导在成骨细胞分化中的作用

基本信息

批准号：
10671739
负责人：
NISHIMURA Riko
金额：
$ 2.11万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671739/
关键词：
Osteoblast IL-6 signaling JAK kinases STAT MAP kinase BMP Smad Cbfa1

项目摘要

1) Role of IL-6 in osteoblastic differentiationWe determined whether IL-6 plays a role in osteoblastogenesis using pluripotent mesenchymal cell line C3H10T1/2. IL-6 induced osteoblastic differentiation of C3H10T1/2 in the presence of sIL-6R, but not in the absence of it. One of IL-6 family cytokine, Oncostatin M also showed quite similar effects on C3H10T1/2. The data suggest that IL-6/sIL-6R is involved in osteoblastic differentiation of pluripotent mesenchymal cells.2) Activation of IL-6 signaling during osteoblactic differentiationTo understand the molecular mechanisms by which IL-6 differentiates C3H10T1/2 into osteoblastic cells, we first determined the intracellular signaling cascade of IL-6 in C3H10T1/2. IL-6/sIL-6R induced tyrosine phosphorylation of gp130, JAK1, and JAK2. STAT1 and STAT3 were tyrosine-phosphorylated by IL-6/sIL-6R treatment, and translocated from cytoplasm into nucleus. IL-6/sIL-6R also activated MAP kinase. These results indicate that IL-6/sIL-6R concomitantl … More y activate JAK/STAT and MAP kinase pathway in C3H10T1/2.3) Role of JAK/STAT and MAP kinase signaling in osteoblastic differentiationIn order to investigate the functional role of JAK/STAT signaling in osteoblastic differentiation, we examined the effects of dominant negative JAK1 (DN-JAK1) or JAK2 (DN-JAK2) on IL-6 induced osteoblastic differentiation. DN-JAK1 as well as DN-JAK2 blocked activation of JAK/STAT signaling. DN-JAK1 and DN-JAK2 also blocked IL-6 induced osteoblastic differentiation of C3H10T1/2. We, next, studied the role of MAP kinases in osteoblastic differentiation using dominant negative ras (DN-ras). DN-ras inhibited activation of MAP kinases. DN-ras partially inhibited activation of STAT and osteoblastic differentiation of C3H10T1/2. The data indicated that essential role of JAK/STAT signaling and the involvement of cross talk between JAK/STAT and MAP kinase signaling in osteoblastic differentiation induced by IL-6.4) BMP2 signaling that regulates osteoblastic differentiationWe found BMP2 induced osteoblastic differentiation by inducing expression of Cbfa1 via activation of Smad signaling. Less

1) IL-6 在成骨细胞分化中的作用我们使用多能间充质细胞系 C3H10T1/2 确定了 IL-6 是否在成骨细胞生成中发挥作用，在 sIL-6R 存在下，IL-6 诱导 C3H10T1/2 的成骨细胞分化，但在 sIL-6R 存在下则不然。 IL-6 家族细胞因子之一制瘤素 M 的缺失对 C3H10T1/2 也表现出非常相似的作用。提示IL-6/sIL-6R参与多能间充质细胞的成骨分化。2)成骨分化过程中IL-6信号的激活为了了解IL-6将C3H10T1/2分化为成骨细胞的分子机制，我们首先确定IL-6 在 C3H10T1/2 中的细胞内信号级联诱导的酪氨酸磷酸化。 gp130、JAK1、STAT1 和 STAT3 通过 IL-6/sIL-6R 处理被酪氨酸磷酸化，并从细胞质转移到细胞核中。这些结果表明 IL-6。 /sIL-6R 伴随的…更多 y 激活 C3H10T1/2.3 中的 JAK/STAT 和 MAP 激酶通路）的作用JAK/STAT 和 MAP 激酶信号在成骨细胞分化中的作用为了研究 JAK/STAT 信号在成骨细胞分化中的功能作用，我们检查了显性失活 JAK1 (DN-JAK1) 或 JAK2 (DN-JAK2) 对 IL-6 诱导的影响。 DN-JAK1 和 DN-JAK2 阻断 JAK/STAT 信号传导，也阻断 IL-6 诱导的成骨细胞分化。接下来，我们使用显性负性 ras (DN-ras) 抑制 MAP 激酶的激活和 C3H10T1 的成骨细胞分化来研究 MAP 激酶的作用。 /2.数据表明JAK/STAT信号传导以及JAK/STAT和MAP激酶信号传导之间的串扰在诱导的成骨细胞分化中的重要作用。 IL-6.4）调节成骨细胞分化的BMP2信号我们发现BMP2通过激活Smad信号诱导Cbfa1的表达来诱导成骨细胞分化。