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Identification of key regulators responsible for dysregulated networks in osteoarthritis by large-scale expression

Song Shi1, Fuyin Wan1, Zhenyu Zhou1

  • 1Department of Orthopaedics, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.

Journal of Orthopaedic Surgery and Research
|April 15, 2021
PubMed
Abstract

Insights

This study identifies key molecular pathways and hub genes involved in osteoarthritis (OA) development. Repurposed drugs, like cardiac glycosides, show promise for novel OA treatment strategies.

Area of Science:

  • Genomics and Molecular Biology
  • Musculoskeletal Disorders Research

Background:

  • Osteoarthritis (OA) is a prevalent global musculoskeletal disorder with limited disease-modifying therapies.
  • Current treatment strategies for OA do not halt disease progression.
  • There is a critical need for novel therapeutic targets and treatment approaches for OA.

Purpose of the Study:

  • To characterize the molecular signatures of osteoarthritis.
  • To identify novel therapeutic targets for osteoarthritis.
  • To explore new treatment strategies for osteoarthritis.

Main Methods:

  • Genome-wide transcriptome data from 132 OA and 74 normal human cartilage/synovium tissues were analyzed.
  • Differential gene expression and functional enrichment analyses identified dysregulated genes and pathways in OA.
  • Computational drug repurposing identified potential therapeutic agents for OA.

Main Results:

  • Key pathways implicated in OA development include extracellular matrix organization, inflammation, bone development, and ossification.
  • Protein-protein interaction network analysis prioritized hub genes such as JUN, CDKN1A, VEGFA, and FOXO3.
  • FDA-approved drugs, including cardiac glycosides, were identified as potential repurposed treatments for OA.

Conclusions:

  • Identified hub genes are proposed to play a role in cartilage homeostasis and represent potential diagnostic and therapeutic targets for OA.
  • Repurposed drugs, specifically cardiac glycosides, offer new therapeutic possibilities for osteoarthritis treatment.
Keywords:
Drug repurposingOsteoarthritisTranscriptional profiling

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