Analysis of intramedullary extramedullary B lymphopoiesis

髓内髓外B淋巴细胞生成分析

基本信息

批准号：
13670318
负责人：
HAYASHI Shinichi
金额：
$ 2.24万
依托单位：
Tottori University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

项目摘要

Using three osteopetrotic mutant mouse strains, which carry reducing bone marrow formation, we have found their B lumphopoiesis lacks in rudimentary bone marrow cavities. The phylogenetical observation supports our finding, suggesting the presence of the relation between osteoclasts and B lymphopoiesis. To be clear the question, this study was performed.The results are shown as follows:1) In bone marrow B lymphopoiesis, Wnt-3a acts stromal cells, resulting in suppressing B lymphopoiesis. However, the factor does not affect osteoclastogenesis.2) Notch signaling is known to inhibit B lymphopoiesis. We assessed the effect of Notch signaling on osteoclastogenesis by using a recombinant ligand, Delta-1. The Notch signaling suppresses osteoclastogenesis directed to osteoclast precursors and through stromal cells, which support osteoclast development.3) Indicating the responsiveness to ligands for toll-like receptors and tumor necrosis factor-α, we demonstrated the presence of distinct osteoclast precursors maintained in each tissue including bone marrow, spleen, peritoneal cavity, and fetal liver.4) We developed the culture system of embryonic stem cells to induce the differentiation of ES cells to osteoclasts, endothelial cells, and osteobasts.Now, we have a model system to study in vitro bone marrow formation.We have already published the papers [1),2),and4)], and the manuscript for 3) has been submitted. Recently, based on our propose, candidate genes for regulating B lymphopoiesis in bone marrow are reported. We will make clear the mechanism of B lymphopoiesis, soon.

使用三个骨质原始突变小鼠菌株，它们带有还原的骨髓形成，我们发现它们的B lumphopoiesis缺乏基本的骨髓腔。系统发明的观察支持我们的发现，表明破骨细胞和B淋巴管菌之间存在关系。需要明确的问题，进行了这项研究。结果如下所示：1）在骨髓B淋巴细胞中，WNT-3A作用于基质细胞，从而抑制了B淋巴细胞。但是，该因子不影响破骨细胞生成。2）已知Notch信号传导抑制B淋巴细胞。我们通过使用重组配体Delta-1评估了Notch信号传导对破骨细胞生成的影响。 The Notch signaling suppresses osteoclast precursors and through stromal cells, which support osteoclast development.3) Indicate the responsiveness to ligands for toll-like receptors and Tumor necrosis factor-α, we demonstrated the presence of distinct osteoclast precursors maintained in each tissue including bone marrow, sleen, peritoneal cavity, and fetal liver.4) We developed the culture system of胚胎干细胞诱导ES细胞对破骨细胞，内皮细胞和骨bast的分化。现在，我们有一个模型系统来研究体外骨髓的形成。我们已经发布了论文[1），4）和4]，以及3）的手稿。最近，根据我们的建议，据报道，骨髓中调节B淋巴管的候选基因。我们将很快清楚地阐明B淋巴细胞的机理。