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Published on: May 25, 2017
Gene Expression Profiles Perturbed by Injury to the Mouse Intervertebral Disc
Ken Chen1, Zuozhen Tian, Huan Wang
1From the Departments of Orthopedic Surgery (KC, HW, LQ) and Physical Medicine & Rehabilitation (ZT, YZ), University of Pennsylvania, Philadelphia, Pennsylvania; Department of Orthopedics, University of Maryland School of Medicine, Baltimore, Maryland (ME-I); Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China (KC); Department of Orthopedic Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, P.R. China (HW); and Section of Rehabilitation Medicine, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania (YZ).
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.
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