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Regulation by adipocytokines of bone metabolism

脂肪细胞因子对骨代谢的调节

基本信息

批准号：
15590970
负责人：
TAKEUCHI Yasuhiro
金额：
$ 2.18万
依托单位：
Okinaka Memorial Institute for Medical Research (2004)The University of Tokyo (2003)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590970/
关键词：
adiponectin bone marrow stromal c osteoblast adipocyte osteocalcin PPARγ leptin

项目摘要

1)Role of adiponectin in differentiation of bone marrow stromal cellsWe examined effects of adiponectin on differentiation of mouse bone marrow stromal cell line ST2. Osteocalcin and PPARγ2 mRNA expressions were determined as osteoblastic and adipocytic differentiation markers, respectively. Cells were stained with Oil-Red O to demonstrate cellular accumulation of triglyceride. Treatment with adiponectin inhibited the expression of osteocalcin mRNA, wheras it had no effects on adipogenesis of ST2 cells. When we examined primary cultures of mouse bone marrow cells, we got essentially the same observations. Therefore, at least in mice, adiponectin seems to inhibit osteoblastic differentiation of bone marrow stromal cells and have no effects on their adipogenesis.2)Analyses of bone obtained from transgenic miceWe next investigated effects of adiponectin on bone in vivo. First, we could not any difference of bone histology in adiponectin-transgenic mice until 10 week of age. Second, heterozygous adiponectin knock-out mice showed no skeletal abnormality at birth. Homozygous knock-out mice were embryonic lethal and have not been investigated in detail in bone histology.3)Role of circulating leptin on bone in vivoRecent report suggests that effects of leptin on central nervous system suppress bone formation in mice through its activation of sympathetic nervous system. We examined effects of changes of circulating leptin levels on bone metabolism in some kinds of transgenic mice. Transgenic mice overexpressing leptin in liver had low bone mass, whereas those overexpressing soluble leptin receptor showed high bone mass. Circulating leptin levels had negative correlation with bone mass in these experimental mice. Thus, it is suggested that circulating leptin also has inhibitory effects on bone formation in vivo.

1)脂联素在骨髓基质细胞分化中的作用观察脂联素对小鼠骨髓基质细胞系ST2分化的影响。骨钙素和PPARγ2mRNA的表达分别作为成骨细胞和脂肪细胞分化的标志物。油红O染色显示细胞内甘油三酯积聚。脂联素可抑制ST2细胞骨钙素mRNA的表达，但对ST2细胞的成脂无影响。当我们检查小鼠骨髓细胞的原代培养时，我们得到了基本上相同的观察结果。因此，至少在小鼠中，脂联素似乎抑制了骨髓基质细胞的成骨分化，并且对它们的脂肪生成没有影响。2)从转基因小鼠获得的骨的分析接下来我们在体内研究了脂联素对骨的影响。首先，在10周龄之前，脂联素转基因小鼠的骨组织学没有任何差异。其次，杂合的脂联素基因敲除小鼠在出生时没有表现出骨骼异常。纯合基因敲除的小鼠是胚胎致死的，骨组织学未见详细研究。3)瘦素在活体骨骼上的作用最近的报道表明，瘦素对中枢神经系统的作用是通过激活交感神经系统抑制小鼠的骨形成。我们检测了几种转基因小鼠循环瘦素水平的变化对骨代谢的影响。在肝脏中高表达瘦素的转基因小鼠骨量较低，而高表达可溶性瘦素受体的转基因小鼠骨量较高。实验小鼠血中瘦素水平与骨量呈负相关。因此，提示循环中的瘦素对体内的骨形成也有抑制作用。

项目成果

期刊论文数量（47）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Recepter tyosine kinases inhibit bone morphogenetic protein-Smad responsive promoter activity and differentiation of murine MC3T3-E1 osteoblast-like cells

受体酪氨酸激酶抑制骨形态发生蛋白-Smad响应启动子活性和小鼠MC3T3-E1成骨细胞样细胞的分化

DOI：
发表时间：
2003
期刊：
J Bone Miner Res 18(5)
影响因子：
0
作者：
Nakayama K;et al.
通讯作者：
et al.

Decreased AP-1 activity and interleukin-11 expression by bone marrow stromal cells may be associated with impaired bone formation in aged mice

骨髓基质细胞 AP-1 活性和白细胞介素 11 表达降低可能与老年小鼠骨形成受损有关

DOI：
发表时间：
2003
期刊：
J Bone Miner Res 518
影响因子：
0
作者：
Toshijima E;et al.
通讯作者：
et al.

Receptor tyrosine kinases inhibit bone morphogenetic protein-Smad responsive promoter activity and osteoblastic differentiation of murine MC3T3-E1 cells.

受体酪氨酸激酶抑制骨形态发生蛋白-Smad 响应启动子活性和小鼠 MC3T3-E1 细胞的成骨细胞分化。

DOI：
发表时间：
2003
期刊：
J Bone Miner Res 18(5)
影响因子：
0
作者：
Nakayama K;Tamura Y;Suzawa M;Harada S;Fukumoto S;Kato M;Miyazono K;Rodan GA;Takeuchi Y;Fujita T.
通讯作者：
Fujita T.

Chikatsu N et al.: "A family of autosomal dominant hypocalcemia with an activating mutation of calcium-sensing receptor gene"Endocr J. 50(1). 91-96 (2003)

Chikatsu N 等人：“具有钙敏感受体基因激活突变的常染色体显性低钙血症家族”Endocr J. 50(1)。

DOI：
发表时间：
期刊：
影响因子：
0
作者：
通讯作者：

Decreased AP-1 activity and interleukin-11 expression by bone marrow stromal cells may be associated with impaired bone formation in aged mice.

骨髓基质细胞 AP-1 活性和白细胞介素 11 表达降低可能与老年小鼠骨形成受损有关。

DOI：
发表时间：
2003
期刊：
J Bone Miner Res 18(8)
影响因子：
0
作者：
Tohjima E;Inoue D;Yamamoto N;Kido S;Ito Y;Kato S;Takeuchi Y;Fukumoto S;Matsumoto T.
通讯作者：
Matsumoto T.