Lumbar Intervertebral Disc mRNA Sequencing Identifies the Regulatory Pathway in Young Adult Patients with Disc Degeneration

INTRODUCTION: The process of intervertebral disc degeneration disease (DDD) is thought to be an age-related phenomenon that includes inflammation and cell apoptosis leading to decreased proteoglycan synthesis with resultant disc dehydration and loss of disc height. It has been reported that 42% of young adults have DDD characterized by a signal change on MRI, it seems beneficial to examine young adults to clarify the process of DDD. METHODS: We performed next generation RNA sequencing on 9 nucleus pulposus (NP) of the lumbar intervertebral disc from young adults (<40 years age, n = 4) and old adults (>40 years of age, n = 5) patients. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analyses were performed to identify the biological functions of differentially expressed mRNAs. RESULTS: A total of 98 genes were found to be significantly upregulated in young adults NP tissue compared to old adults NP tissue. These upregulated mRNAs were primarily involved in signal peptide, collagen, and extracellular matrix organization. Among the top upregulated genes such as LGALS1, COL6A2 and PTMS may have the key regulatory functions related to early age disc degeneration. In addition, we found 346 genes were significantly downregulated in young adults NP tissue compared to old adults NP tissue. They were primarily involved in glycoprotein, membrane, and immunoglobulin-like fold. CONCLUSION: This investigation provides a comprehensive overview of mRNA expression in the nucleus pulposus of intervertebral disc tissue in young adult patients compare with old adult patients. By applying computational analyses to our large dataset of human clinical specimens, we have been able to identify candidate gene regulatory networks that act in early age disc degeneration.