title: P53 functional abnormality in mesenchymal stem cells promotes osteosarcoma development.
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.
authors.affiliation: 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.
authors.forename: T
authors.initials: T
authors.lastname: Velletri
authors.affiliation: 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.
authors.forename: N
authors.initials: N
authors.lastname: Xie
authors.affiliation: 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.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Y
authors.initials: Y
authors.lastname: Huang
authors.affiliation: 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.
authors.forename: Q
authors.initials: Q
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Q
authors.initials: Q
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: P
authors.identifier: http://orcid.org/0000-0001-7685-7471
authors.initials: P
authors.lastname: Shou
authors.affiliation: 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.
authors.forename: Y
authors.initials: Y
authors.lastname: Gan
authors.affiliation: 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.
authors.forename: G
authors.initials: G
authors.lastname: Cao
authors.affiliation: Biochemistry Laboratory IDI-IRCC, Department of Experimental Medicine and Surgery, University of Rome Torvergata, Rome 00133, Italy.|Medical Research Council, Toxicology Unit, Leicester University, Leicester LE1 9HN, UK.
authors.forename: G
authors.initials: G
authors.lastname: Melino
authors.affiliation: 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.|Soochow Institutes for Translational Medicine, Soochow University, Suzhou, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Shi
mesh_terms: D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology; D002454:Cell Differentiation; D002478:Cells, Cultured; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D012516:Osteosarcoma / Q000235:genetics* / Q000473:pathology