Potential genes and pathways associated with heterotopic ossification derived from analyses of gene expression profiles

Zhanyu Yang,Xin Li,Rui Guan,Delong Liu,Bin Sheng,Yiwei Wang

doi:10.1186/s13018-021-02658-1

Abstract

BackgroundHeterotopic 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.MethodsGene 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.ResultsIn 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.ConclusionsThis 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.

Highlights

Heterotopic ossification (HO) represents pathological lesions that refer to the development of heterotopic bone in extraskeletal tissues around joints
Data source and data preprocessing As large amounts of data were integrated into a gene expression profile (GSE94683), the original data were downloaded from the Gene Expression Omnibus (GEO) database
In the biological process (BP) ontology, the majority of differentially expressed genes (DEGs), including Ephrin B3 (EFNB3), Unc-5 netrin receptor C (UNC5C), TMEFF2, Parathyroid hormone 2 (PTH2), Mast/stem cell growth factor receptor kit (KIT), Fibroblast growth factor 13 (FGF13), and WNT1 inducible signaling pathway (WISP3) were intensively enriched in cell signal transmission items, including axon guidance (9 genes), negative regulation of cell migration (7 genes), peptidyl-tyrosine phosphorylation (6 genes), and cell-cell signaling (10 genes)

Summary

Introduction

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. Heterotopic ossification (HO) represents pathological lesions, referred to as the development of heterotopic bone in extraskeletal tissues around joints, which often occurs in the elbow, thigh, pelvis, and shoulder [1, 2]. The clinical manifestations were altered with the progression of the disease. Progressive ossifying fibrous dysplasia (FOP), a genetic hereditary form of HO, is extremely rare, with a prevalence of approximately 1:2,000,000 in the population [4,5,6,7]. There was a much higher incidence of HO following softtissue trauma, amputations, and central nervous system injury, such as cerebral anoxia, encephalitis, traumatic brain injuries, and spinal cord lesions [8, 9]

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