Differentiation of Mesenchymal Stem Cells in Bone Marrow

骨髓间充质干细胞的分化

• 批准号: 12557082
• 负责人: SUDA Toshio
• 金额: $ 8.45万
• 依托单位: Keio University (2002)Kumamoto University (2000-2001)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12557082/
• 关键词: osteoblast; osteoclast; RANK; ALCAM; mesenchymal stem cell; perichondrium; vascular invasion; ephrin-B2; 造血幹細胞; アンジオポエチンファミリー; 血管新生; 骨髄間葉組織; Side Population; ALCAM接着分子; 造骨・破骨; 造血環境; 骨髄造血; RANK; アンジオポエチン; ARPs

We studied the linkage among osteogenesis, angiogenesis and hematopoiesis in bone marrow formation. Interaction between osteoclasts and osteoblasts is indispensable to form bone and bone cavity as hematopoietic tissues. RANK/RANKL provided new insights into the osteoclast differentiation pathway. We have established a pure osteoclast culture system by isolating precursor cells and cultured in the presence of M-CSF and soluble RANKL. This system revealed that differentiation of osteoclasts is anchorage-dependent and that osteoclastogenesis is completely inhibited by GM-CSF and switched to dendritic cell differentiation by suppression of c-Fos expression. On the other hand, we purified mesenchymal stem cells from perichondrial cells and characterized their differentiation. We show that chondrocytes inhibited the growth of vascular endothelial cells. Eph-ephrin signaling might be involved in the invasion of vascular cells. Now, we are trying to isolate osteoclast-specific molecules by DNA subtraction method between osteoclasts and macrophages derived from common precursor cells. Since these two types of cells express quite similar molecules, osteoclast-specific molecules are enriched. These osteoclast-specific molecules are targets to regulate the osteoclast function.

我们研究了骨髓形成中骨生成、血管生成和造血之间的联系。破骨细胞和成骨细胞之间的相互作用是形成骨和骨腔等造血组织所必需的。RANK/RANKL为破骨细胞分化途径提供了新的见解。我们通过分离前体细胞并在M-CSF和可溶性RANKL存在下培养，建立了纯破骨细胞培养系统。该系统揭示了破骨细胞的分化是锚定依赖性的，并且破骨细胞生成被GM-CSF完全抑制，并且通过抑制c-Fos表达而切换到树突状细胞分化。另一方面，我们从软骨膜细胞中纯化间充质干细胞并鉴定其分化。我们发现，软骨细胞抑制血管内皮细胞的生长。Eph-ephrin信号通路可能参与了血管细胞的侵袭。目前，我们正试图通过DNA消减法从破骨细胞和巨噬细胞中分离出破骨细胞特异性分子。由于这两种类型的细胞表达非常相似的分子，因此富含破骨细胞特异性分子。这些破骨细胞特异性分子是调节破骨细胞功能的靶点。

项目成果

Nosaka K: "Mechanism of hypercalcemia in adult T-cell leukemia : overexpression of receptor activator of nuclear factor κB ligand on adult T-cell leukemia cells"Blood. 99. 634-640 (2002)

野坂 K：“成人 T 细胞白血病高钙血症的机制：核因子 κB 配体的受体激活剂在成人 T 细胞白血病细胞上的过度表达”Blood. 99. 634-640 (2002)

Zhang X-Q: "Stromal cells expressing ephrin-B2 promote the growth and sprouting of ephrin-B2^+ endothelial cells."Blood. (in press). (2001)

张X-Q：“表达ephrin-B2的基质细胞促进ephrin-B2^内皮细胞的生长和出芽。”血液。

Arai F et al.: "Mesenchymal stem cells in perichondrium express activated cell adhesion molecule and participate in bone formation."J. Exp. Med. 195. 1449-1563 (2002)

Arai F等人：“软骨膜中的间充质干细胞表达活化的细胞粘附分子并参与骨形成。”J.

Nomiyama H: "Organization of the chemokine genes in the human and mouse major clusters of CC and CXC chemokines : diversification between the two species"Genes and Immunity. 2. 110-113 (2001)

Nomiyama H：“人类和小鼠 CC 和 CXC 趋化因子主要簇中趋化因子基因的组织：两个物种之间的多样化”基因与免疫。

Takakura N: "A role for hematopoietic cells in promoting angiogenesis."Cell. 102. 199-209 (2000)

Takakura N：“造血细胞在促进血管生成中的作用。”细胞。