ArticleBMC musculoskeletal disorders2023
GREM1, LRPPRC and SLC39A4 as potential biomarkers of intervertebral disc degeneration: a bioinformatics analysis based on multiple microarray and single-cell sequencing data.
Article in BMC musculoskeletal disorders, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 3 citations in OpenAlex.
- LINC00324 induces nucleus pulposus cell apoptosis in intervertebral disc degeneration via miR-143-3p targeted TRAIL/DR4/DR5 axis.Biology direct · 2026Article
- Mendelian randomization analysis identifies HLA-A and AP2M1 as genetic biomarkers linked to immune-endocytic crosstalk in intervertebral disc degeneration.Journal of cell communication and signaling · 2026Article
- Bioinformatic analysis of glycosylation-related genes in intervertebral disc degeneration and their roles in immune infiltration and diagnostic models.Scientific reports · 2025Article
- Current cutting-edge omics techniques on musculoskeletal tissues and diseases.Bone research · 2025Review
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundLow back pain (LBP) has drawn much widespread attention and is a major global health concern. In this field, intervertebral disc degeneration (IVDD) is frequently the focus of classic studies. However, the mechanistic foundation of IVDD is unclear and has led to conflicting outcomes.
methodsGene expression profiles (GSE34095, GSE147383) of IVDD patients alongside control groups were analyzed to identify differentially expressed genes (DEGs) in the GEO database. GSE23130 and GSE70362 were applied to validate the yielded key genes from DEGs by means of a best subset selection regression. Four machine-learning models were established to assess their predictive ability. Single-sample gene set enrichment analysis (ssGSEA) was used to profile the correlation between overall immune infiltration levels with Thompson grades and key genes. The upstream targeting miRNAs of key genes (GSE63492) were also analyzed. A single-cell transcriptome sequencing data (GSE160756) was used to define several cell clusters of nucleus pulposus (NP), annulus fibrosus (AF), and cartilaginous endplate (CEP) of human intervertebral discs and the distribution of key genes in different cell clusters was yielded.
resultsBy developing appropriate p-values and logFC values, a total of 6 DEGs was obtained. 3 key genes (LRPPRC, GREM1, and SLC39A4) were validated by an externally validated predictive modeling method. The ssGSEA results indicated that key genes were correlated with the infiltration abundance of multiple immune cells, such as dendritic cells and macrophages. Accordingly, these 4 key miRNAs (miR-103a-3p, miR-484, miR-665, miR-107) were identified as upstream regulators targeting key genes using the miRNet database and external GEO datasets. Finally, the spatial distribution of key genes in AF, CEP, and NP was plotted. Pseudo-time series and GSEA analysis indicated that the expression level of GREM1 and the differentiation trajectory of NP chondrocytes are generally consistent. GREM1 may mainly exacerbate the degeneration of NP cells in IVDD.
conclusionsOur study gives a novel perspective for identifying reliable and effective gene therapy targets in IVDD.
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