Regulation of chicken mesenchymal stem cells by bioactive molecules

生物活性分子对鸡间充质干细胞的调控

• 批准号: 402169-2011
• 负责人: Kim, WooKyun
• 金额: $ 2.33万
• 依托单位: University of Manitoba
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2012
• 资助国家: 加拿大
• 起止时间: 2012-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=505970
• 关键词: Regulation; chicken; mesenchymal; stem; cells

Mesenchymal stem cells (MSC) are multipotent progenitor cells that are present in blood, bone, adipose tissue, muscle, and cartilage. MSC are common progenitors of osteoblasts and adipocytes, and a reciprocal relationship between osteogenic and adipogenic differentiation of MSC has been demonstrated. The control of lineage specific differentiation of MSC into specific cell types is achieved through specific master regulators of gene expression such as peroxisome proliferator-activated receptor gamma (PPAR-gamma) for adipocyte differentiation and Runx2 for osteoblast differentiation. Better understanding of bioactive molecules that regulate such master regulators of differentiation is vital to enhance our current knowledge of MSC regulation and improve animal growth and skeletal health. Specific oxysterols are potential bioactive molecules that can regulate MSC differentiation. Oxysterols, a large family of 27-carbon oxygenated products of cholesterol, are present in the circulation and tissues of human and animal. I have reported that specific oxysterols inhibit the adipogenic differentiation of mouse MSC by inhibiting the expression of PPAR-gamma, the master regulator of adipogenesis, while inducing osteogenic differentiation in these cells. Recently, I found that pro-osteogenic and anti-adipogenic effects of specific oxysterols are mediated through Hh and/or Notch signalling activation in mouse MSC. Since Hh and Notch signaling pathways are conservative among animal species, it is important to understand the regulation of chicken MSC by Hh and Notch pathway activation by specific oxysterols. The long-term goal of the proposed research is to understand the regulation of chicken mesenchymal stem cells by bioactive molecules and to determine the impact of mesenchymal stem cells on animal growth and health. I believe that my research will provide better understanding of the molecular mechanisms by which bioactive molecules regulate osteogenic and adipogenic differentiation of MSC and have significant implications for expanding the basic knowledge of MSC regulation for general biological sciences.

间充质干细胞（MSC）是血液，骨骼，脂肪组织，肌肉和软骨中存在的多能祖细胞。 MSC是成骨细胞和脂肪细胞的常见祖细胞，已经证明了MSC的成骨和脂肪生成分化之间的相互关系。通过基因表达的特定主调节剂，例如过氧化物酶体增殖物激活的受体伽马（PPAR-GAMMA）来控制MSC对特定细胞类型的谱系特异性分化，以实现脂肪细胞分化和runx2，以进行成骨细胞分化。对调节这种分化的主要调节剂的生物活性分子的更好理解对于增强我们当前对MSC调节的了解并改善动物的生长和骨骼健康至关重要。特定的氧甲醇是可以调节MSC分化的潜在生物活性分子。氧化酚是胆固醇的27碳氧化产物的大家族，存在于人类和动物的循环和组织中。我报道说，特定的氧甲醇通过抑制脂肪形成的主要调节剂PPAR-GAMMA的表达来抑制小鼠MSC的成脂分化，同时诱导这些细胞中的成骨分化。最近，我发现特异性氧甲醇的促骨和抗掺杂作用是通过HH和/或小鼠MSC中的Notch信号传导介导的。由于HH和Notch信号传导途径在动物物种中是保守的，因此重要的是要通过特定的氧甲醇来了解HH和Notch途径激活鸡肉MSC。拟议的研究的长期目标是通过生物活性分子了解鸡间充质干细胞的调节，并确定间充质干细胞对动物生长和健康的影响。我认为，我的研究将更好地理解生物活性分子调节MSC的成骨和成脂分化的分子机制，并对扩展MSC调节的一般生物学科学的基本知识具有重要意义。