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Analysis of long non-coding RNA expression profiles in disuse osteoporosis using microarray and bioinformatics.

W Z Wei1,2, B Li1, J X Lin2

  • 1Department of Joints, Tianjin Hospital, Tianjin University, Tianjin, China.

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|July 23, 2021
PubMed
Summary

Disuse osteoporosis (DOP) is a consequence of spaceflight and immobility. This study identifies key long non-coding RNAs (lncRNAs) and potential therapeutic compounds, revealing new mechanisms for DOP development and treatment.

Keywords:
Bone Mesenchymal Stem Cells (BMSCs)Connectivity Map (CMAP)bioinformaticsdisuse osteoporosislong non-coding RNAsmiR-361-3p

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Area of Science:

  • Biomedical Sciences
  • Genomics
  • Space Medicine

Background:

  • Disuse osteoporosis (DOP) is a significant health concern resulting from prolonged immobility, such as in spaceflight or spinal cord injuries.
  • Bone marrow mesenchymal stem cells (BMSCs) are crucial for bone homeostasis, and their dysregulation in osteogenic differentiation can lead to orthopedic diseases.
  • The precise molecular mechanisms underlying DOP remain incompletely understood.

Purpose of the Study:

  • To elucidate the molecular mechanisms of disuse osteoporosis (DOP) by analyzing gene expression data.
  • To identify differentially expressed long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) involved in DOP.
  • To discover potential therapeutic targets and compounds for treating DOP.

Main Methods:

  • Utilized R's limma package to identify differentially expressed mRNAs and lncRNAs from Gene Expression Omnibus (GEO) datasets (GSE100930, GSE17696).
  • Constructed a coding-non-coding gene co-expression (CNC) network to analyze interactions between lncRNAs and mRNAs.
  • Performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, and Connectivity Map (CMap) analysis for drug discovery.

Main Results:

  • Identified 2,212 differentially expressed mRNAs (DEmRNAs) and 22 differentially expressed lncRNAs (DElncRNAs).
  • The CNC network highlighted GSNAS1, SNHG12, and EPB41LA4A-AS1 as key lncRNAs potentially regulating DOP.
  • Connectivity Map analysis identified scoulerine, kinetin riboside, and dexanabinol as potential therapeutic agents for DOP.

Conclusions:

  • Discovered a novel mechanism for bone marrow mesenchymal stem cell lineage shifts under microgravity, contributing to DOP.
  • Established a link between protein-coding mRNAs and ncRNAs in the pathogenesis of DOP.
  • The findings offer potential avenues for developing new therapeutic strategies for disuse osteoporosis.