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: 2011
• 资助国家: 加拿大
• 起止时间: 2011-01-01 至 2012-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=487963
• 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)是存在于血液、骨、脂肪组织、肌肉和软骨中的多能祖细胞。间充质干细胞是成骨细胞和脂肪细胞的共同前体细胞，其成骨和成脂分化之间存在相互作用关系。MSC向特定细胞类型的谱系特异性分化是通过特定的基因表达调控实现的，如用于脂肪细胞分化的PPAR-γ和用于成骨细胞分化的Runx2。更好地了解调控这种主要分化调节因子的生物活性分子，对于增强我们目前对MSC调控的知识，改善动物生长和骨骼健康至关重要。特异性氧化甾醇是一种潜在的生物活性分子，可以调节MSC的分化。氧化甾醇是胆固醇的27碳氧化产物大家族，存在于人和动物的循环和组织中。我曾报道，特定的氧固醇通过抑制脂肪生成的主要调节因子PPAR-γ的表达而抑制小鼠MSC的成脂分化，同时诱导这些细胞的成骨分化。最近，我发现特定的氧化甾醇的促成骨和抗成脂作用是通过激活HH和/或Notch信号在小鼠MSC上介导的。由于HH和Notch信号通路在动物物种中是保守的，因此了解HH对鸡MSC的调控以及特定的氧固醇激活Notch通路是很重要的。这项研究的长期目标是了解生物活性分子对鸡间充质干细胞的调控，并确定间充质干细胞对动物生长和健康的影响。相信本研究将对生物活性分子调控间充质干细胞成骨和成脂分化的分子机制有更好的认识，对拓展普通生物科学对间充质干细胞调控的基础知识具有重要意义。