Gene expression profile analysis of human intervertebral disc degeneration

Abstract

In this study, we used microarray analysis to investigate the biogenesis and progression of intervertebral disc degeneration. The gene expression profiles of 37 disc tissue samples obtained from patients with herniated discs and degenerative disc disease collected by the National Cancer Institute Cooperative Tissue Network were analyzed. Differentially expressed genes between more and less degenerated discs were identified by significant analysis of microarray. A total of 555 genes were significantly overexpressed in more degenerated discs with a false discovery rate of < 3%. Functional annotation showed that these genes were significantly associated with membrane-bound vesicles, calcium ion binding and extracellular matrix. Protein-protein interaction analysis showed that these genes, including previously reported genes such as fibronectin, COL2A1 and β-catenin, may play key roles in disc degeneration. Unsupervised clustering indicated that the widely used morphology-based Thompson grading system was only marginally associated with the molecular classification of intervertebral disc degeneration. These findings indicate that detailed, systematic gene analysis may be a useful way of studying the biology of intervertebral disc degeneration.

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

“…The novel AF markers brain abundant membrane attached signal protein 1 (BASP1), sclerostin domain containing 1 (SOSTDC1), 18 glypican 3 (GPC3), and pleiotrophin (PTN) 44 also showed co-regulation with AF related ECM gene networks. Our study did not show a clear link to either AF or NP phenotypes for several published markers including CD24 antigen (CD24), keratin 8 (KRT8), keratin 18 (KRT18), keratin 19 (KRT19), cadherin 2 (CDH2), 17 carbonic anhydrase 12 (CA12), 45 and hypoxia inducible factor 1 alpha subunit (HIF1A), 13,14,46 all of which showed co-regulation with gene networks unrelated to disk phenotype. Protein levels do not always correlate with mRNA expression, which could explain some of the differences between our study and previous investigations.…”

“…[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.…”

Aberrantly expressed long noncoding RNAs in human intervertebral disc degeneration: a microarray related study

“…DAVID functional annotation clustering was employed for the functional annotation of the mRNAs. Among the clusters, terms of membrane-bound vesicles were also noted, which pertain to upregulated genes in IDD development [ 33 ]. Interestingly, several other clusters were observed in our study, including apoptosis and negative regulation of gene expression.…”

Molecular Biology and Interactions in Intervertebral Disc Development, Homeostasis, and Degeneration, with Emphasis on Future Therapies: A Systematic Review

“…Another study using microarray and proteinprotein interaction analyses showed that the upregulation of fibronectin, COL2A1 and β-catenin genes could be related to degeneration of the IVD. However, the application of unsupervised clustering in that study showed that the widely-used Thompson grading system demonstrated a marginal association with the molecular classification of IVD degeneration (Chen et al, 2013). Fibulin, a regulator of ADAMTS-1, is upregulated in degenerative human NP (Pattappa et al, 2012).…”