Integrated transcriptome and proteome analyses identify novel regulatory network of nucleus pulposus cells in intervertebral disc degeneration
Abstract Background Degeneration of intervertebral disc is a major cause of lower back pain and neck pain. Studies have tried to unveil the regulatory network using either transcriptomic or proteomic analysis. However, neither have fully elucidated the exact mechanism of degeneration process. Since...
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doaj-5b707e9320e046dc8cade40ae347c61b2021-04-02T21:07:11ZengBMCBMC Medical Genomics1755-87942021-02-0114111210.1186/s12920-021-00889-zIntegrated transcriptome and proteome analyses identify novel regulatory network of nucleus pulposus cells in intervertebral disc degenerationChen Xu0Shengchang Luo1Leixin Wei2Huiqiao Wu3Wei Gu4Wenchao Zhou5Baifeng Sun6Bo Hu7Hongyu Zhou8Yang Liu9Huajiang Chen10Xiaojian Ye11Wen Yuan12Spine Center, Department of Orthopaedics, Changzheng Hospital, Naval Medical UniversitySpine Center, Department of Orthopaedics, Changzheng Hospital, Naval Medical UniversitySpine Center, Department of Orthopaedics, Changzheng Hospital, Naval Medical UniversitySpine Center, Department of Orthopaedics, Changzheng Hospital, Naval Medical UniversitySpine Center, Department of Orthopaedics, Changzheng Hospital, Naval Medical UniversitySpine Center, Department of Orthopaedics, Changzheng Hospital, Naval Medical UniversitySpine Center, Department of Orthopaedics, Changzheng Hospital, Naval Medical UniversitySpine Center, Department of Orthopaedics, Changzheng Hospital, Naval Medical UniversitySpine Center, Department of Orthopaedics, Changzheng Hospital, Naval Medical UniversitySpine Center, Department of Orthopaedics, Changzheng Hospital, Naval Medical UniversitySpine Center, Department of Orthopaedics, Changzheng Hospital, Naval Medical UniversityMicrosurgery Center, Department of Orthopaedics, Changzheng Hospital, Naval Medical UniversitySpine Center, Department of Orthopaedics, Changzheng Hospital, Naval Medical UniversityAbstract Background Degeneration of intervertebral disc is a major cause of lower back pain and neck pain. Studies have tried to unveil the regulatory network using either transcriptomic or proteomic analysis. However, neither have fully elucidated the exact mechanism of degeneration process. Since post-transcriptional regulation may affect gene expression by modulating the translational process of mRNA to protein product, a combined transcriptomic and proteomic study may provide more insight into the key regulatory network of Intervertebral disc degeneration. Methods In order to obtain the proteomic and transcriptomic data, we performed label-free proteome analysis on freshly isolated nucleus pulposus cells and obtained transcriptome profiling data from the Gene Expression Omnibus repository. To identify the key regulatory network of intervertebral disc degeneration in nucleus pulposus cells, we performed bioinformatic analyses and established a protein-RNA interacting network. To validate the candidate genes, we performed in vitro experimentation and immunochemistry labeling to identify their potential function during nucleus pulposus degeneration. Results The label-free proteome analysis identified altogether 656 proteins, and 503 of which were differentially expressed between nucleus pulposus cells from degenerated or normal disc cells. Using the existing nucleus pulposus transcriptomic profiling data, we integrated the proteomic and transcriptomic data of nucleus pulposus cells, and established a protein-RNA interacting network to show the combined regulatory network of intervertebral disc degeneration. In the network, we found 9 genes showed significant changes, and 6 of which (CHI3L1, KRT19, COL6A2, DPT, TNFAIP6 and COL11A2) showed concordant changes in both protein and mRNA level. Further functional analysis showed these candidates can significantly affect the degeneration of the nucleus pulposus cell when altering their expression. Conclusions This study is the first to use combined analysis of proteomic and transcriptomic profiling data to identify novel regulatory network of nucleus pulposus cells in intervertebral disc degeneration. Our established protein-RNA interacting network demonstrated novel regulatory mechanisms and key genes that may play vital roles in the pathogenesis of intervertebral disc degeneration.https://doi.org/10.1186/s12920-021-00889-zIntervertebral disc degenerationNucleus pulposusProteomicsTranscriptomeBioinformatic analysis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Chen Xu Shengchang Luo Leixin Wei Huiqiao Wu Wei Gu Wenchao Zhou Baifeng Sun Bo Hu Hongyu Zhou Yang Liu Huajiang Chen Xiaojian Ye Wen Yuan |
spellingShingle |
Chen Xu Shengchang Luo Leixin Wei Huiqiao Wu Wei Gu Wenchao Zhou Baifeng Sun Bo Hu Hongyu Zhou Yang Liu Huajiang Chen Xiaojian Ye Wen Yuan Integrated transcriptome and proteome analyses identify novel regulatory network of nucleus pulposus cells in intervertebral disc degeneration BMC Medical Genomics Intervertebral disc degeneration Nucleus pulposus Proteomics Transcriptome Bioinformatic analysis |
author_facet |
Chen Xu Shengchang Luo Leixin Wei Huiqiao Wu Wei Gu Wenchao Zhou Baifeng Sun Bo Hu Hongyu Zhou Yang Liu Huajiang Chen Xiaojian Ye Wen Yuan |
author_sort |
Chen Xu |
title |
Integrated transcriptome and proteome analyses identify novel regulatory network of nucleus pulposus cells in intervertebral disc degeneration |
title_short |
Integrated transcriptome and proteome analyses identify novel regulatory network of nucleus pulposus cells in intervertebral disc degeneration |
title_full |
Integrated transcriptome and proteome analyses identify novel regulatory network of nucleus pulposus cells in intervertebral disc degeneration |
title_fullStr |
Integrated transcriptome and proteome analyses identify novel regulatory network of nucleus pulposus cells in intervertebral disc degeneration |
title_full_unstemmed |
Integrated transcriptome and proteome analyses identify novel regulatory network of nucleus pulposus cells in intervertebral disc degeneration |
title_sort |
integrated transcriptome and proteome analyses identify novel regulatory network of nucleus pulposus cells in intervertebral disc degeneration |
publisher |
BMC |
series |
BMC Medical Genomics |
issn |
1755-8794 |
publishDate |
2021-02-01 |
description |
Abstract Background Degeneration of intervertebral disc is a major cause of lower back pain and neck pain. Studies have tried to unveil the regulatory network using either transcriptomic or proteomic analysis. However, neither have fully elucidated the exact mechanism of degeneration process. Since post-transcriptional regulation may affect gene expression by modulating the translational process of mRNA to protein product, a combined transcriptomic and proteomic study may provide more insight into the key regulatory network of Intervertebral disc degeneration. Methods In order to obtain the proteomic and transcriptomic data, we performed label-free proteome analysis on freshly isolated nucleus pulposus cells and obtained transcriptome profiling data from the Gene Expression Omnibus repository. To identify the key regulatory network of intervertebral disc degeneration in nucleus pulposus cells, we performed bioinformatic analyses and established a protein-RNA interacting network. To validate the candidate genes, we performed in vitro experimentation and immunochemistry labeling to identify their potential function during nucleus pulposus degeneration. Results The label-free proteome analysis identified altogether 656 proteins, and 503 of which were differentially expressed between nucleus pulposus cells from degenerated or normal disc cells. Using the existing nucleus pulposus transcriptomic profiling data, we integrated the proteomic and transcriptomic data of nucleus pulposus cells, and established a protein-RNA interacting network to show the combined regulatory network of intervertebral disc degeneration. In the network, we found 9 genes showed significant changes, and 6 of which (CHI3L1, KRT19, COL6A2, DPT, TNFAIP6 and COL11A2) showed concordant changes in both protein and mRNA level. Further functional analysis showed these candidates can significantly affect the degeneration of the nucleus pulposus cell when altering their expression. Conclusions This study is the first to use combined analysis of proteomic and transcriptomic profiling data to identify novel regulatory network of nucleus pulposus cells in intervertebral disc degeneration. Our established protein-RNA interacting network demonstrated novel regulatory mechanisms and key genes that may play vital roles in the pathogenesis of intervertebral disc degeneration. |
topic |
Intervertebral disc degeneration Nucleus pulposus Proteomics Transcriptome Bioinformatic analysis |
url |
https://doi.org/10.1186/s12920-021-00889-z |
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