Regulation by adipocytokines of bone metabolism

脂肪细胞因子对骨代谢的调节

• 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

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）脂联素在分化骨髓基质中的作用，研究了脂联素对小鼠骨髓基质细胞系ST2的分化的影响。骨钙素和PPARγ2mRNA表达分别确定为成骨细胞和脂肪细胞分化标记。用油红色O染色细胞，以证明甘油三酸酯的细胞积累。脂联素治疗抑制骨钙素mRNA的表达，当它对ST2细胞的脂肪形成没有影响时。当我们检查小鼠骨髓细胞的原代培养物时，我们的观察结果基本相同。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细胞分化，并且对它们的脂肪生成没有影响。2）对从转基因小鼠获得的骨骼分析下一步研究了脂联蛋白对体内骨骼对骨的影响。首先，直到10周龄，我们在脂联素 - 转基因小鼠中无法造成任何差异。其次，杂合脂联蛋白敲除小鼠出生时没有骨骼异常。纯合子敲除小鼠是胚胎致死的，尚未在骨组织学中进行详细研究。3）循环瘦素在骨骼中的作用在VivoreCent报告中的作用表明，瘦素对中枢神经系统的影响通过其交感神经系统的激活来抑制小鼠的骨形成。我们检查了循环瘦素水平变化对某些转基因小鼠中骨代谢的影响。过表达瘦素的转基因小鼠的骨骼质量低，而过表达的固体瘦素受体表现出较高的骨骼质量。循环瘦素水平与这些实验小鼠的骨骼质量负相关。这就是建议循环瘦素对体内骨形成也具有抑制作用。

项目成果

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

• 发表时间: 2003
• 期刊: J Bone Miner Res 18(5)
• 作者: Nakayama K;et al.
• 通讯作者: et al.

Targeted ablation of Fgf23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism

• DOI: 10.1172/jci200419081
• 发表时间: 2004-02-01
• 期刊: JOURNAL OF CLINICAL INVESTIGATION
• 影响因子: 15.9
• 作者: Shimada, T;Kakitani, M;Yamashita, T
• 通讯作者: Yamashita, T

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。

• 发表时间: 2003
• 期刊: J Bone Miner Res 18(8)
• 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.

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。

• 发表时间: 2003
• 期刊: J Bone Miner Res 18(5)
• 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.

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

• 发表时间: 2003
• 期刊: J Bone Miner Res 518
• 作者: Toshijima E;et al.
• 通讯作者: et al.