Gene Markers of Fracture Healing in Early Stage and the Regulatory Mechanism During the Process Using Microarray Analysis

Overview

Journal Acta Orthop Traumatol Turc

Specialties Emergency Medicine
Orthopedics

Date 2016 Dec 14

PMID 27956081

Citations 1

Authors

Chengxue Wang

Baochang Qi

Lei Tan

Jieping Cheng

Affiliations

Soon will be listed here.

Abstract

Background: The aim of this study was to explore crucial markers and uncover the regulatory mechanisms of fracture healing in the early stage.

Methods: Gene expression profile of GSE45156 was downloaded, in which 3 fractured samples and 3 unfractured samples were used in our present study. Based on the threshold value, differentially expressed genes (DEGs) were selected between two kinds of samples using limma package in R. Enrichment analysis of these DEGs was performed by DAVID software. Furthermore, protein-protein interaction (PPI) network was established integrating information in STRING database, and visualized by Cytoscape software.

Results: We identified a set of 960 DEGs including 509 up-regulated and 451 downregulated genes. Biological processes involving RNA splicing and cell cycle were significantly enriched for the up-regulated genes such as Snrpd2, Eftud2, Plk1 and Bub1b, whereas skeletal system development and bone development processes were predominant for down-regulated genes like Ubc. In the constructed PPI network, all the five genes were the predominant nodes, of which Snrpd2 was linked to Eftud2, while Bub1b was to interact with Plk1.

Conclusion: Five candidate genes crucial for indicating the process of fracture in early stage were identified. Eftud2, Snrpd2, Bub1b and Plk1 might function through the involvement of cell-cycle-related BP, while Ubc might influence the protein degradation during bone development. However, more experimental validations are needed to confirm these results.

Citing Articles

Significance of Spliceosome-Related Genes in the Prediction of Prognosis and Treatment Strategies for Lung Adenocarcinoma.

Yang Y, Huang T, Fan Y, Lu H, Shao J, Wang Y Biomed Res Int. 2022; 2022:1753563.

PMID: 36389112 PMC: 9652092. DOI: 10.1155/2022/1753563.

References

Smoot M, Ono K, Ruscheinski J, Wang P, Ideker T . Cytoscape 2.8: new features for data integration and network visualization. Bioinformatics. 2010; 27(3):431-2. PMC: 3031041. DOI: 10.1093/bioinformatics/btq675. View

Hede K . Which came first? Studies clarify role of aneuploidy in cancer. J Natl Cancer Inst. 2005; 97(2):87-9. DOI: 10.1093/jnci/97.2.87. View

Liu R, Birke O, Morse A, Peacock L, Mikulec K, Little D . Myogenic progenitors contribute to open but not closed fracture repair. BMC Musculoskelet Disord. 2011; 12:288. PMC: 3266223. DOI: 10.1186/1471-2474-12-288. View

Giannoudis P, Einhorn T, Marsh D . Fracture healing: the diamond concept. Injury. 2008; 38 Suppl 4:S3-6. DOI: 10.1016/s0020-1383(08)70003-2. View

Ellis P, Dawson M, Dixon M . Mutation testing in Treacher Collins Syndrome. J Orthod. 2002; 29(4):293-7; discussion 278. DOI: 10.1093/ortho/29.4.293. View

Rambaldi D, Felice B, Praz V, Bucher P, Cittaro D, Guffanti A . Splicy: a web-based tool for the prediction of possible alternative splicing events from Affymetrix probeset data. BMC Bioinformatics. 2007; 8 Suppl 1:S17. PMC: 1885846. DOI: 10.1186/1471-2105-8-S1-S17. View

Chang J, Li C, Liao H, Wang C, Wang G, Ho M . Anti-inflammatory drugs suppress proliferation and induce apoptosis through altering expressions of cell cycle regulators and pro-apoptotic factors in cultured human osteoblasts. Toxicology. 2009; 258(2-3):148-56. DOI: 10.1016/j.tox.2009.01.016. View

Zhang J, Wiemann S . KEGGgraph: a graph approach to KEGG PATHWAY in R and bioconductor. Bioinformatics. 2009; 25(11):1470-1. PMC: 2682514. DOI: 10.1093/bioinformatics/btp167. View

Tian C, Liu D, Sun Q, Chen C, Xu Y, Wang H . Comparative analysis of gene expression profiles between cortex and thalamus in Chinese fatal familial insomnia patients. Mol Neurobiol. 2013; 48(1):36-48. DOI: 10.1007/s12035-013-8426-6. View

10.

Hecht J, Kuhl H, Haas S, Bauer S, Poustka A, Lienau J . Gene identification and analysis of transcripts differentially regulated in fracture healing by EST sequencing in the domestic sheep. BMC Genomics. 2006; 7:172. PMC: 1578570. DOI: 10.1186/1471-2164-7-172. View

11.

Trost Z, Trebse R, Prezelj J, Komadina R, Logar D, Marc J . A microarray based identification of osteoporosis-related genes in primary culture of human osteoblasts. Bone. 2009; 46(1):72-80. DOI: 10.1016/j.bone.2009.09.015. View

12.

Harris M, Clark J, Ireland A, Lomax J, Ashburner M, Foulger R . The Gene Ontology (GO) database and informatics resource. Nucleic Acids Res. 2003; 32(Database issue):D258-61. PMC: 308770. DOI: 10.1093/nar/gkh036. View

13.

Li X, Wang H, Touma E, Qi Y, Rousseau E, Quigg R . TP508 accelerates fracture repair by promoting cell growth over cell death. Biochem Biophys Res Commun. 2007; 364(1):187-93. DOI: 10.1016/j.bbrc.2007.07.202. View

14.

Pape H, Marcucio R, Humphrey C, Colnot C, Knobe M, Harvey E . Trauma-induced inflammation and fracture healing. J Orthop Trauma. 2010; 24(9):522-5. DOI: 10.1097/BOT.0b013e3181ed1361. View

15.

Stuermer A, Hoehn K, Faul T, Auth T, Brand N, Kneissl M . Mouse pre-replicative complex proteins colocalise and interact with the centrosome. Eur J Cell Biol. 2006; 86(1):37-50. DOI: 10.1016/j.ejcb.2006.09.002. View

16.

Dennis Jr G, Sherman B, Hosack D, Yang J, Gao W, Lane H . DAVID: Database for Annotation, Visualization, and Integrated Discovery. Genome Biol. 2003; 4(5):P3. View

17.

Ai-Aql Z, Alagl A, Graves D, Gerstenfeld L, Einhorn T . Molecular mechanisms controlling bone formation during fracture healing and distraction osteogenesis. J Dent Res. 2008; 87(2):107-18. PMC: 3109437. DOI: 10.1177/154405910808700215. View

18.

Czakai K, Muller K, Mosesso P, Pepe G, Schulze M, Gohla A . Perturbation of mitosis through inhibition of histone acetyltransferases: the key to ochratoxin a toxicity and carcinogenicity?. Toxicol Sci. 2011; 122(2):317-29. PMC: 3155084. DOI: 10.1093/toxsci/kfr110. View

19.

Guan Y, Yang X, Yang W, Charbonneau C, Chen Q . Mechanical activation of mammalian target of rapamycin pathway is required for cartilage development. FASEB J. 2014; 28(10):4470-81. PMC: 4202102. DOI: 10.1096/fj.14-252783. View

20.

Whitfield M, Sherlock G, Saldanha A, Murray J, Ball C, Alexander K . Identification of genes periodically expressed in the human cell cycle and their expression in tumors. Mol Biol Cell. 2002; 13(6):1977-2000. PMC: 117619. DOI: 10.1091/mbc.02-02-0030. View