The Regulation of osteobiastogenesis and adipogenesis by BMP2

BMP2 对成骨和脂肪生成的调节

• 批准号: 12671804
• 负责人: NISHIMURA Riko
• 金额: $ 2.05万
• 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: 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/grant/KAKENHI-PROJECT-12671804/
• 关键词: Osteoblast; Adipocytes; C; EBPβ; BMP2; LIP; Cbfa1; PPARγ

(1) Role of C/EBF beta in the differentiation of mesenchymal stem cells into osteoblasts and adipocytesWe found that C/EBP beta was expressed in mature osteoblasts as well as adipocytes, we, therefore, examined the role of C/EBP beta in osteoblastogenesis by overexpressing C/EBP beta using adenovirus technology. Overexpression of C/EBP beta able to induce the differentiation of mesenchymal stem cells into not only adipocytes but also osteoalasts. Furthermore, overexpression of C/EBP beta induced osteocalcin expression and transactivated osteocaicin promoter. The data indicated that C/EBP beta is an important transcription factor for osteoblast differentiation of mesenchymal cells.(2) Cooperative role of C/EBP beta and Cbfal in osteoblast differentiationWe, next, evaluated the relationship between C/EBP beta and Cbfa1 that is a critical transcription factor in bone formation and osteoblastogenesis, and found that C/EBP beta physically associated with Cbfa1. More importantly, osteogenic action of Cbfa1 was further enhanced by overexpression of C/EBP beta, showing the important role of cooperation between C/EBP beta and Cbfa1 during osteoblast differentiation.(3) Reciprocal role of C/EBP beta isoform, LIP, in osteoblastogenesis and adipogenesisAn isoform of C/EBP beta, LIP, was also expressed in mature osteoblasts, suggesting the role of LIP during osteoblastogenesis. Overexpression of LIP blocks the adipogenesis in a dominant-negative fashion, but exhibits osteogenic action as a co-factor for Cbfa1. Our data provide the new insight into the understanding the molecular mechanisms that determine the direction of mesenchymal stem cells in bone.

(1)C/EBFβ在骨髓间充质干细胞向成骨细胞和脂肪细胞分化中的作用我们发现C/EBPβ在成骨细胞和脂肪细胞中都有表达，因此，我们通过腺病毒技术过表达C/EBPβ来研究C/EBPβ在成骨细胞形成中的作用。C/EBPβ过表达可诱导间充质干细胞分化为脂肪细胞和成骨细胞。此外，C/EBPβ过表达可诱导骨钙素表达和反式激活骨钙素启动子。结果表明，C/EBPβ是间充质细胞向成骨细胞分化的重要转录因子。(2)C/EBPβ与Cbfal在成骨细胞分化中的协同作用接下来，我们研究了C/EBPβ与Cbfa1的关系，发现C/EBPβ与Cbfa1在物理上具有相关性。更重要的是，C/EBPβ的过度表达进一步增强了Cbfa1的成骨作用，表明C/EBPβ与Cbfa1在成骨细胞分化过程中的协同作用。(3)C/EBPβ亚型LIP在成骨细胞发生和成脂过程中的相互作用C/EBPβ亚型LIP在成熟成骨细胞中也有表达，提示LIP在成骨细胞形成中的作用。LIP的过度表达以显性-负性方式阻止脂肪形成，但作为Cbfa1的辅助因子表现出成骨作用。我们的数据为理解决定骨髓间充质干细胞在骨中的方向的分子机制提供了新的见解。

项目成果

Ji X et al.: "Patterns of gene expression associated with BMP-2-induced osteoblast and adipocyte differentiation of mesenchymal progenitor cell 3T3-F442A"J Bone Miner Met. 18. 132-139 (2000)

Ji X等：“与BMP-2诱导的间充质祖细胞3T3-F442A成骨细胞和脂肪细胞分化相关的基因表达模式”J Bone Miner Met。

Michigami T: "Cell-cell contact between marrow stromal cells and myeloma cells via VCAM-1 and α4β1 integrin enhances production of osteoclast-stimulating activity in culture"Blood. 96. 1953-1960 (2000)

Michigami T：“骨髓基质细胞和骨髓瘤细胞之间通过 VCAM-1 和 α4β1 整合素的细胞接触增强了培养物中破骨细胞刺激活性的产生”Blood。

Yoneda T: "Cellular and molecular basis of preferential metastasis of breast cancer to bone."J Orthop Sci. 5. 75-81 (2000)

Yoneda T：“乳腺癌优先转移至骨的细胞和分子基础。”J Orthop Sci。

Marzia M, et al: "Decreased c-src expression enhances osteoblast differentiation and bone formation."J Cell Biol. 151. 311-320 (2000)

Marzia M 等人：“c-src 表达减少可增强成骨细胞分化和骨形成。”J Cell Biol。

Toshiyuki Yoneda et al: "Cellular and molecular basis of preferential metastasis of breast cancer to bone."J Orthop Sci. 5. 75-81 (2000)

Toshiyuki Yoneda 等人：“乳腺癌优先转移至骨的细胞和分子基础。”J Orthop Sci。