Abstract
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.
Highlights
P53 is a guardian of cell differentiation
We found that the higher secretion of nitric oxide (NO) from p53-deficient mesenchymal stem cells (MSCs) have an inhibitory effect on T cells, and promote tumor growth.[128]
P53 regulates the genomic stability of MSCs and their osteogenic differentiation functioning as ‘bone remodeling surveillant’ to prevent bone tumor initiation
Summary
TP53 belongs to the so-called ‘p53 gene family’ of transcription factors, which includes the proteins p63, p73, and p53 itself.[1,2,3] Having been discovered since 1979, p53 is the most studied member of the family with over 60 000 papers so far published. Efforts, and advances in knowledge, many crucial intriguing points still remain unanswered to fully understand the physiological and pathological role of p53 These wide range of effects raise from several angles, including, for example, its regulation at the transcriptional level, at the level of micro-RNA,[19,20,21,22] and splicing isoforms[23,24] to its translational regulation and its stability/degradation at the protein level.[25,26,27,28,29] In parallel to so much effort in understanding the function of p53, significant efforts are underway on its potential clinical exploit ation.[30,31,32,33,34,35,36,37] being identified after ~ 20 years, already p63 and p73 show a similar complexity, and the
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
