Identification of Biomarkers That Modulate Osteogenic Differentiation in Mesenchymal Stem Cells Related to Inflammation and Immunity: A Bioinformatics-Based Comprehensive Study

被引:7
作者
Feng, Ziyi [1 ]
Su, Xin [1 ]
Wang, Ting [1 ]
Guo, Shu [1 ]
机构
[1] China Med Univ, Hosp 1, Dept Plast Surg, 155 Nanjing North St, Shenyang 110002, Peoples R China
关键词
bioinformatics; osteogenic differentiation; mesenchymal stem cells; biomarker; immunity; inflammation; STROMAL CELLS;
D O I
10.3390/ph15091094
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Background: Inducing mesenchymal stem cells (MSCs) osteogenesis may be beneficial in a number of clinical applications. The aim of this study is to identify key novel biomarkers of this process and to analyze the possible regulatory effects on inflammation and immunity. Results: Seven datasets (GSE159137, GSE159138, GSE114117, GSE88865, GSE153829, GSE63754, GSE73087) were obtained from the Gene Expression Omnibus database and were assigned to either the training or the validation dataset. The least absolute shrinkage and selection operator (LASSO) logistic regression model was applied to the training data to select biomarkers of osteogenesis, which were then confirmed using the validation dataset. FK506 binding protein 5 (FKBP5), insulin-like growth factor binding protein (IGFBP2), prostaglandin E receptor 2 (PTGER2), SAM domain and HD domain-containing protein 1 (SAMHD1), and transmembrane tetratricopeptide 1 (TMTC1) were highlighted as potential biomarkers. In addition, the differential expressions of immunity and inflammation-related genes were examined and their correlations with the five identified biomarkers were analyzed. The results from performing RT-qPCR and Western blots confirmed that the levels of each of these biomarkers were all significantly increased following osteogenic differentiation of MSCs. Conclusions: Our results identify five biomarkers related to MSCs osteogenesis and allow us to identify their potential roles in immunoregulation and inflammation. Each biomarker was verified by in vitro experiments.
引用
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页数:20
相关论文
共 44 条
[1]   Extracellular matrix dynamics during mesenchymal stem cells differentiation [J].
Assis-Ribas, Thais ;
Forni, Maria Fernanda ;
Brochado Winnischofer, Sheila Maria ;
Sogayar, Mari Cleide ;
Trombetta-Lima, Marina .
DEVELOPMENTAL BIOLOGY, 2018, 437 (02) :63-74
[2]   Adipose-derived stem cell therapies for bone regeneration [J].
Barba, Marta ;
Di Taranto, Giuseppe ;
Lattanzi, Wanda .
EXPERT OPINION ON BIOLOGICAL THERAPY, 2017, 17 (06) :677-689
[3]   Mesenchymal Stromal Cells: Sensors and Switchers of Inflammation [J].
Bernardo, Maria Ester ;
Fibbe, Willem E. .
CELL STEM CELL, 2013, 13 (04) :392-402
[4]   Fate decision of mesenchymal stem cells: adipocytes or osteoblasts? [J].
Chen, Q. ;
Shou, P. ;
Zheng, C. ;
Jiang, M. ;
Cao, G. ;
Yang, Q. ;
Cao, J. ;
Xie, N. ;
Velletri, T. ;
Zhang, X. ;
Xu, C. ;
Zhang, L. ;
Yang, H. ;
Hou, J. ;
Wang, Y. ;
Shi, Y. .
CELL DEATH AND DIFFERENTIATION, 2016, 23 (07) :1128-1139
[5]   SAMHD1 Suppression of Antiviral Immune Responses [J].
Chen, Shuliang ;
Bonifati, Serena ;
Qin, Zhihua ;
St Gelais, Corine ;
Wu, Li .
TRENDS IN MICROBIOLOGY, 2019, 27 (03) :254-267
[6]   SAMHD1 suppresses innate immune responses to viral infections and inflammatory stimuli by inhibiting the NF-κB and interferon pathways [J].
Chen, Shuliang ;
Bonifati, Serena ;
Qin, Zhihua ;
St Gelais, Corine ;
Kodigepalli, Karthik M. ;
Barrett, Bradley S. ;
Kim, Sun Hee ;
Antonucci, Jenna M. ;
Ladner, Katherine J. ;
Buzovetsky, Olga ;
Knecht, Kirsten M. ;
Xiong, Yong ;
Yount, Jacob S. ;
Guttridge, Denis C. ;
Santiago, Mario L. ;
Wu, Li .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2018, 115 (16) :E3798-E3807
[7]   Mitochondrial transfer from MSCs to T cells induces Treg differentiation and restricts inflammatory response [J].
Court, Angela C. ;
Le-Gatt, Alice ;
Luz-Crawford, Patricia ;
Parra, Eliseo ;
Aliaga-Tobar, Victor ;
Batiz, Luis Federico ;
Contreras, Rafael A. ;
Ortuzar, Maria Ignacia ;
Kurte, Monica ;
Elizondo-Vega, Roberto ;
Maracaja-Coutinho, Vinicius ;
Pino-Lagos, Karina ;
Figueroa, Fernando E. ;
Khoury, Maroun .
EMBO REPORTS, 2020, 21 (02)
[8]   Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement [J].
Dominici, M. ;
Le Blanc, K. ;
Mueller, I. ;
Slaper-Cortenbach, I. ;
Marini, F. C. ;
Krause, D. S. ;
Deans, R. J. ;
Keating, A. ;
Prockop, D. J. ;
Horwitz, E. M. .
CYTOTHERAPY, 2006, 8 (04) :315-317
[9]   Conserved sequence motifs in human TMTC1, TMTC2, TMTC3, and TMTC4, new O-mannosyltransferases from the GT-C/PMT clan, are rationalized as ligand binding sites [J].
Eisenhaber, Birgit ;
Sinha, Swati ;
Jadalanki, Chaitanya K. ;
Shitov, Vladimir A. ;
Tan, Qiao Wen ;
Sirota, Fernanda L. ;
Eisenhaber, Frank .
BIOLOGY DIRECT, 2021, 16 (01)
[10]   Effects of prostaglandin E2 and D2 on cell proliferation and osteogenic capacity of human mesenchymal stem cells [J].
Ern, C. ;
Frasheri, I ;
Berger, T. ;
Kirchner, H. G. ;
Heym, R. ;
Hickel, R. ;
Folwaczny, M. .
PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS, 2019, 151 :1-7