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Identification of Therapeutic Targets for Osteoporosis through Multiomics Integration and the Potential Dual Role of

Jun Du1, Minjun Chang2, Kunlong Jiang2

  • 1Department of Orthopedic Magnetic Resonance Chamber, The First Affiliated Hospital of Soochow University, No. 899 Pinghai Road, Suzhou 215000, China.

Journal of Chemical Information and Modeling
|June 27, 2025
PubMed

Insights

This study reveals the androgen receptor's (AR) dual role in osteoporosis, identifying AR antagonists as promising treatments. Targeting AR signaling with drugs like cyproterone acetate may effectively combat bone resorption.

Area of Science:

  • Biomedical research
  • Genomics
  • Pharmacology

Background:

  • Osteoporosis involves complex cellular and molecular mechanisms.
  • Androgen receptor (AR) signaling is implicated in bone pathophysiology, but its precise role is not fully understood.

Purpose of the Study:

  • To investigate potential therapeutic targets for osteoporosis using a multiomics approach.
  • To explore the dual role of androgen receptor (AR) signaling in osteoporosis.
  • To identify effective drug candidates for treating bone resorption.

Main Methods:

  • Analysis of single-cell RNA sequencing data (GSE147287) to identify cell types and developmental trajectories.
  • Differential miRNA analysis and integrated database analysis to identify hub genes.
  • Construction of drug-gene-miRNA interaction networks, including DeepPurpose analysis, drug MoA, and molecular docking.
  • In vitro experiments to assess drug efficacy on osteoclastogenesis.

Main Results:

  • Nine major cell types and their trajectories were identified in osteoporosis samples.
  • Nineteen dysregulated miRNAs and six hub genes, including AR, were identified.
  • AR is highly expressed in tissue stem cells and involved in myeloid cell activation and osteoclast differentiation.
  • Cyproterone acetate (AR antagonist) showed stronger binding affinity to AR and superior inhibition of osteoclastogenesis compared to norethisterone (AR agonist).

Conclusions:

  • Androgen receptor (AR) signaling plays a dual role in osteoporosis pathophysiology.
  • Targeting AR with antagonists, such as cyproterone acetate, presents a promising therapeutic strategy for osteoporosis and bone resorption.

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