Zinc Finger Protein Zac1 and Chondrogenesis

锌指蛋白 Zac1 和软骨形成

• 批准号: 6803601
• 负责人: MON-LI H. CHU
• 金额: $ 7.85万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-25 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6803601
• 关键词: RNA; cartilage development; cell differentiation; cell growth regulation; cell proliferation; gene expression; microarray technology; northern blottings; polymerase chain reaction; protein structure; regeneration

DESCRIPTION (provided by applicant): The long-term objective of this application is to understand the molecular and cellular mechanisms underlying cartilage formation and repair. Degeneration of the joint cartilage leads to osteoarthritis (OA), the most common form of arthritis affecting middle-aged and elderly people. The cartilage loss is caused, at least in part, by the failure of chondrocytes to repair the cartilage matrix and reduced proliferative capacity of the chondrocytes. The mechanisms that regulate chondrocyte proliferation and its biosynthetic activity, however, are poorly understood. The applicant has found that Zacl, a recently characterized zinc finger protein, is predominantly localized in the developing chondrogenic tissue during mouse embryogenesis. Zacl possesses anti-proliferative activity and is a potential tumor suppressor gene, suggesting that it may have a role in regulating chondrocyte proliferation and differentiation, and cartilage gene expression. This application proposes to investigate the role of Zacl in chondrogenesis using an established in vitro model culture system for chondrocyte differentiation. The effects of over-expression and inhibition of Zacl during in vitro chondrogenesis will be studied, and the genes regulated by Zacl in chondrocyte differentiation will be investigated. These studies will provide a better understanding of regulatory factors important for cartilage formation and repair.

描述（由申请人提供）：本申请的长期目标是了解软骨形成和修复的分子和细胞机制。关节软骨的退化导致骨关节炎（OA），这是影响中老年人的最常见的关节炎形式。软骨损失至少部分是由软骨细胞修复软骨基质的失败和软骨细胞增殖能力的降低引起的。然而，调节软骨细胞增殖及其生物合成活性的机制知之甚少。本申请人已经发现，Zacl，一种最近表征的锌指蛋白，在小鼠胚胎发生期间主要定位于发育中的软骨形成组织中。Zacl具有抗增殖活性，是一种潜在的肿瘤抑制基因，提示其可能在调节软骨细胞增殖和分化以及软骨基因表达方面发挥作用。本申请提出使用用于软骨细胞分化的已建立的体外模型培养系统来研究Zacl在软骨形成中的作用。将研究Zacl在体外软骨形成过程中的过表达和抑制的作用，并将研究在软骨细胞分化中由Zacl调节的基因。这些研究将提供一个更好的了解调节因素的重要软骨形成和修复。