Potential Genes and Pathways Associated with Heterotopic Ossification Derived from Analyses of Gene Expression Profiles

Overview

Journal J Orthop Surg Res

Publisher Biomed Central

Specialty Orthopedics

Date 2021 Aug 14

PMID 34389038

Citations 4

Authors

Zhanyu Yang

Delong Liu

Rui Guan

Xin Li

Yiwei Wang

Bin Sheng

Affiliations

Soon will be listed here.

Abstract

Background: Heterotopic ossification (HO) represents pathological lesions that refer to the development of heterotopic bone in extraskeletal tissues around joints. This study investigates the genetic characteristics of bone marrow mesenchymal stem cells (BMSCs) from HO tissues and explores the potential pathways involved in this ailment.

Methods: Gene expression profiles (GSE94683) were obtained from the Gene Expression Omnibus (GEO), including 9 normal specimens and 7 HO specimens, and differentially expressed genes (DEGs) were identified. Then, protein-protein interaction (PPI) networks and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed for further analysis.

Results: In total, 275 DEGs were differentially expressed, of which 153 were upregulated and 122 were downregulated. In the biological process (BP) category, the majority of DEGs, including EFNB3, UNC5C, TMEFF2, PTH2, KIT, FGF13, and WISP3, were intensively enriched in aspects of cell signal transmission, including axon guidance, negative regulation of cell migration, peptidyl-tyrosine phosphorylation, and cell-cell signaling. Moreover, KEGG analysis indicated that the majority of DEGs, including EFNB3, UNC5C, FGF13, MAPK10, DDIT3, KIT, COL4A4, and DKK2, were primarily involved in the mitogen-activated protein kinase (MAPK) signaling pathway, Ras signaling pathway, phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) signaling pathway, and Wnt signaling pathway. Ten hub genes were identified, including CX3CL1, CXCL1, ADAMTS3, ADAMTS16, ADAMTSL2, ADAMTSL3, ADAMTSL5, PENK, GPR18, and CALB2.

Conclusions: This study presented novel insight into the pathogenesis of HO. Ten hub genes and most of the DEGs intensively involved in enrichment analyses may be new candidate targets for the prevention and treatment of HO in the future.

Citing Articles

NCBI GEO: archive for gene expression and epigenomics data sets: 23-year update.

Clough E, Barrett T, Wilhite S, Ledoux P, Evangelista C, Kim I Nucleic Acids Res. 2023; 52(D1):D138-D144.

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The role of miRNA and lncRNA in heterotopic ossification pathogenesis.

Pulik L, Mierzejewski B, Sibilska A, Grabowska I, Ciemerych M, Legosz P Stem Cell Res Ther. 2022; 13(1):523.

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Case Report: Unusual Heterotopic Ossification of the Hindfoot.

Danya F, Marco B, Valentino C, Mario M, Antonio Pompilio G Front Surg. 2022; 9:917560.

PMID: 35747430 PMC: 9209653. DOI: 10.3389/fsurg.2022.917560.

Heterotopic ossification vs. fracture healing: Extracellular vesicle cargo proteins shed new light on bone formation.

Hrkac S, Novak R, Salai G, Grazio S, Vlahovic T, Grgurevic L Bone Rep. 2022; 16:101177.

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