Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University, School of Medicine, 320 Yueyang Road, Shanghai 200031, China.
Biochemistry Laboratory IDI-IRCC, Department of Experimental Medicine and Surgery, University of Rome Torvergata, Rome 00133, Italy.
Cell Death Dis. 2016 Jan 21;7(1):e2015. doi: 10.1038/cddis.2015.367.
It has been shown that p53 has a critical role in the differentiation and functionality of various multipotent progenitor cells. P53 mutations can lead to genome instability and subsequent functional alterations and aberrant transformation of mesenchymal stem cells (MSCs). The significance of p53 in safeguarding our body from developing osteosarcoma (OS) is well recognized. During bone remodeling, p53 has a key role in negatively regulating key factors orchestrating the early stages of osteogenic differentiation of MSCs. Interestingly, changes in the p53 status can compromise bone homeostasis and affect the tumor microenvironment. This review aims to provide a unique opportunity to study the p53 function in MSCs and OS. In the context of loss of function of p53, we provide a model for two sources of OS: MSCs as progenitor cells of osteoblasts and bone tumor microenvironment components. Standing at the bone remodeling point of view, in this review we will first explain the determinant function of p53 in OS development. We will then summarize the role of p53 in monitoring MSC fidelity and in regulating MSC differentiation programs during osteogenesis. Finally, we will discuss the importance of loss of p53 function in tissue microenvironment. We expect that the information provided herein could lead to better understanding and treatment of OS.
已经表明，p53 在各种多能祖细胞的分化和功能中起着关键作用。p53 突变可导致基因组不稳定，随后导致间充质干细胞（MSCs）的功能改变和异常转化。p53 对于保护我们的身体免受骨肉瘤（OS）的发展的重要性是众所周知的。在骨重塑过程中，p53 在负调控调控 MSC 成骨分化早期的关键因子中起着关键作用。有趣的是，p53 状态的变化会破坏骨内稳态并影响肿瘤微环境。这篇综述旨在提供一个研究 p53 在 MSCs 和 OS 中的功能的独特机会。在 p53 功能丧失的情况下，我们为两种 OS 来源提供了一个模型：作为成骨细胞祖细胞的 MSC 和骨肿瘤微环境成分。从骨重塑的角度来看，在这篇综述中，我们将首先解释 p53 在 OS 发展中的决定性功能。然后，我们将总结 p53 在监测 MSC 保真度和调节成骨过程中的 MSC 分化程序中的作用。最后，我们将讨论 p53 功能丧失在组织微环境中的重要性。我们期望本文提供的信息可以帮助我们更好地理解和治疗 OS。
