Integrated transcriptome and proteome analyses identifies novel genes and regulatory networks in intervertebral disc degeneration

Background: Intervertebral disc degeneration is a major cause of symptoms like low back pain and neck pain. Many groups have tried to reveal the regulatory network using either transcriptome or proteome profiling technologies, however, the relationship between these differentially expressed proteins and mRNAs are not elucidated. Since post-transcriptional regulation and other mechanisms may affect the translation of mRNA to protein, a combined transcriptome and proteome study may give more precise data on unveiling important regulatory network and key genes of Intervertebral disc degeneration. Results: In the present study, we used the label-free quantification proteomic approach and identify 656 proteins expressed in either degenerated or normal nucleus pulposus, of which 503 proteins are differentially expressed. Taking advantage of the existing nucleus pulposus transcriptome data, we combine and reanalyze the data and find 105 differentially expressed mRNA between degenerated and normal nucleus pulposus. By comparing these data, only 9 genes show significant changes in both protein and mRNA data, while 6 genes (TNFAIP6, CHI3L1, KRT19, DPT, COL6A2 and COL11A2) show concordant changes in both protein and mRNA level. Further functional analyses show different functions of the altered mRNAs and proteins in degeneration, indicating great difference between protein network and mRNA network. Using the gene co-expression network method, we uncover novel regulatory network and potential genes that may play vital roles in intervertebral disc degeneration by combining protein and mRNA data. Conclusions: This is the first study to identify novel regulatory network of intervertebral disc degeneration using combined analysis of both transcriptome and proteome, which may give new insight into the molecular mechanism of intervertebral disc degeneration.