Nkx3.2 nuclear localization and cartlidge formation

描述（由申请人提供）： 关节炎是一种广泛的衰弱性疾病，其中关节软骨变得解体。体外再生软骨可能是治疗这些疾病的合理方法之一。了解软骨如何降解以及如何通过生物工程产生新的软骨需要彻底了解软骨形成过程中发生的信号事件。我们的长期目标是揭示胚胎中控制软骨形成的机制，这将为治疗关节炎和其他骨骼疾病提供知识。本研究的目的是探讨软骨形成过程中Nkx3.2表达和核定位的调控。我们的中心假设是Nkx3.2的控制是软骨分化的关键机制。我们将通过追求以下具体目标来测试我们的假设：1。探讨促软骨形成信号Shh、BMP和Sox 9调控Nkx3.2核定位的机制。2.检测软骨抑制信号TNF-α和IL-1 β对Nkx3.2表达和核定位的影响。3.确定Nkx3.2是否促进人类间充质干细胞的软骨分化。Nkx3.2是一种重要的蛋白质，因为它不仅促进软骨形成，而且还防止软骨细胞肥大。因此，Nkx3.2是引入祖细胞以促进永久软骨形成的合理候选物。了解这种蛋白的调节将有助于我们在我们未来的研究中将Nkx3.2引入成体干细胞，以指导和维持分化的软骨细胞表型，在我们的奋进软骨生物工程，并开发治疗关节炎。

DESCRIPTION (provided by applicant): Arthritis is a widespread debilitating disease in which the joint cartilage becomes disintegrated. Regenerating cartilage in vitro may be part of a plausible treatment for these conditions. The understanding how cartilage is degraded and how to produce new cartilage through bioengineering requires a thorough understanding of the signaling events that take place during cartilage formation. Our long-range goal is to unveil the mechanisms that govern cartilage formation in the embryo, which will provide the knowledge for treating arthritis and other skeletal diseases. The objective of this proposal is to investigate the regulation of Nkx3.2 expression and nuclear localization during chondrogenesis. Our central hypothesis is that the control of Nkx3.2 is a key mechanism to cartilage differentiation. We will test our hypothesis by pursuing the following Specific Aims: 1. Investigate the mechanisms of Nkx3.2 nuclear localization controlled by pro-chondrogenic signals Shh, BMP and Sox9. 2. Examine the effect of cartilage-inhibiting signals TNF-a and IL-1 (i on Nkx3.2 expression and nuclear localization. 3. Determine if Nkx3.2 promotes cartilage differentiation in human mesenchymal stem cells. Nkx3.2 is an important protein because it not only promotes cartilage formation, but also prevents chondrocyte hypertrophy. Thus, Nkx3.2 is a plausible candidate to be introduced into the progenitor cells in order to promote the formation of permanent cartilage. Understanding the regulation of this protein will help us in our future research of introducing Nkx3.2 in adult stem cells to direct and maintain differentiated chondrocyte phenotype in our endeavor of cartilage bioengineering, and on developing remedies for arthritis.