Microarray analysis of genes and gene functions in disc degeneration

Abstract

The aim of the present study was to screen differentially expressed genes (DEGs) in human degenerative intervertebral discs (IVDs), and to perform functional analysis on these DEGs. The gene expression profile was downloaded from the Gene Expression Omnibus database (GSE34095)and included six human IVD samples: three degenerative and three non-degenerative. The DEGs between the normal and disease samples were identified using R packages. The online software WebGestalt was used to perform the functional analysis of the DEGs, followed by Osprey software to search for interactions between the DEGs. The Database for Annotation, Visualization and Integrated Discovery was utilized to annotate the DEGs in the interaction network and then the DEGs were uploaded to the Connectivity Map database to search for small molecules. In addition, the active binding sites for the hub genes in the network were obtained, based on the Universal Protein database. By comparing the gene expression profiles of the non-degenerative and degenerative IVDs, the DEGs between the samples were identified. The DEGs were significantly associated with transforming growth factor β and the extracellular matrix. Matrix metalloproteinase 2 (MMP2) was identified as the hub gene of the interaction network of DEGs. In addition, MMP2 was found to be upregulated in degenerative IVDs. The screened small molecules and the active binding sites of MMP2 may facilitate the development of methods to inhibit overexpression of MMP2.

Defining the phenotype of young healthy nucleus pulposus cells: Recommendations of the Spine Research Interest Group at the 2014 annual ORS meeting

“…Very recent studies have used bioinformatics approaches to identify specific gene networks that change with aging. It was noted that differentially expressed genes with aging and degeneration are associated with membrane‐bound vesicles, calcium‐ion binding, MAPK and Rho families, and TGF‐β and extracellular matrix networks, particularly focused around MMP2 . While important for understanding the pathogenesis of degeneration, the usefulness of such studies in this discussion is limited due to the lack of NP‐cell specificity of these proteins.…”

RNA sequencing identifies gene regulatory networks controlling extracellular matrix synthesis in intervertebral disk tissues

“…[8][9][10][11][12][13][14] Studies evaluating transcriptome data using microarrays have provided us with an initial understanding of the molecular mechanisms underlying disk biology and have played a major role in helping to identify important biologic markers specific for AF and NP disk tissues. [15][16][17][18][19] However, knowledge regarding the regulatory role of molecular factors and how they contribute to tissue homeostasis still requires further study.…”

Identification of the potential molecular targets for human intervertebral disc degeneration based on bioinformatic methods

“…The cartilaginous endplates contain the peripheral vasculature, which can nourish the disc (1). The main morphological manifestations of IDD are vertebral instability, disc herniation and spinal stenosis (8). Significant changes in morphology, structure and composition are accompanied by specific changes in the disc with aging and degeneration, including alteration of the elastic modulus and swelling pressure of the nucleus pulposus (9).…”

“…Additionally, Tang et al (8) demonstrated that differentially expressed genes (DEGs) identified in degenerative disc tissue samples were mainly associated with transforming growth factor-β and the ECM. Furthermore, Wang et al (19) reported that deregulated miR-155 could promote Fas-mediated apoptosis in human IDD by targeting Fas-associated death domain-containing protein (FADD) and caspase-3.…”