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HOXC10 Regulates Osteogenesis of Mesenchymal Stromal Cells Through Interaction with Its Natural Antisense Transcript

Bingzong Li1, Huiying Han2, Sha Song2

  • 1Department of Haematology, The Second Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.

Stem Cells (Dayton, Ohio)
|October 25, 2018
PubMed

Insights

Long non-coding RNA HOXC-AS3 enhances HOXC10 expression, impairing osteogenic differentiation in mesenchymal stromal cells from multiple myeloma patients. Targeting HOXC-AS3 may treat bone loss in multiple myeloma.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • Mesenchymal stromal cells (MSCs) from multiple myeloma (MM) patients exhibit impaired osteogenic differentiation.
  • Long non-coding RNAs (lncRNAs) are implicated in oncogenic pathways and cellular regulation.
  • The specific molecular mechanisms behind impaired osteogenesis in MM-MSCs require further elucidation.

Purpose of the Study:

  • To investigate the role of lncRNA HOXC-AS3 in the osteogenic differentiation of bone marrow-derived MSCs (BM-MSCs) from MM patients.
  • To elucidate the interaction between HOXC-AS3 and HOXC10 and its effect on osteogenesis.
  • To evaluate the therapeutic potential of targeting HOXC-AS3 in MM-related bone loss.

Main Methods:

  • Identification and characterization of HOXC-AS3 in MM-MSCs.
  • Analysis of the interaction between HOXC-AS3 and HOXC10.
  • Assessment of HOXC-AS3's impact on osteogenic differentiation in vitro.
  • In vivo studies using mouse models with systemically administered siHOXC-AS3 to evaluate bone loss prevention.

Main Results:

  • lncRNA HOXC-AS3 was identified in MM-MSCs and interacts with HOXC10, increasing its stability and expression.
  • HOXC-AS3 overexpression repressed osteogenic differentiation in MM-MSCs.
  • Intravenous administration of siHOXC-AS3 prevented bone loss in mouse models by promoting bone formation and reducing catabolism.
  • HOXC-AS3 enhances HOXC10 expression, which is crucial for osteogenesis in BM-MSCs.

Conclusions:

  • lncRNA HOXC-AS3 plays a critical role in regulating osteogenesis in BM-MSCs by upregulating HOXC10 expression.
  • HOXC-AS3 contributes to impaired osteogenic differentiation in MM-MSCs.
  • lncHOXC-AS3 represents a potential therapeutic target for treating bone diseases associated with multiple myeloma.
Keywords:
Antisense oligonucleotidesBone marrowDifferentiationMesenchymal stromal cellsOsteoblast

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