Gene Expression Profiles Perturbed by Injury to the Mouse Intervertebral Disc.

Abstract

OBJECTIVES: Back pain subsequent to intervertebral disc injury is a common clinical problem. Previous work examining early molecular changes post injury mainly used a candidate marker approach. In this study, gene expression in the injured and intact mouse tail intervertebral discs was determined with a nonbiased whole transcriptome approach. DESIGN: Mouse tail intervertebral disc injury was induced by a needle puncture. Whole murine transcriptome was determined by RNASeq. Transcriptomes of injured intervertebral discs were compared with those of intact controls by bioinformatic methods. RESULTS: Among the 18,078 murine genes examined, 592 genes were differentially expressed ( P.adj < 0.01). Novel genes upregulated in injured compared with intact intervertebral discs included Chl1, Lum , etc. Ontology study of upregulated genes revealed that leukocyte migration was the most enriched biological process, and network analysis showed that Tnfa had the most protein-protein interactions. Novel downregulated genes in the injured intervertebral discs included 4833412C05Rik , Myoc , etc . The most enriched downregulated pathways were related to cytoskeletal organization. CONCLUSIONS: Novel genes highly regulated after disc injury were identified with an unbiased approach; they may serve as biomarkers of injury and response to treatments in future experiments. Enriched biological pathways and molecules with high numbers of connections may be targets for treatments after injury.