Expression of FBXW11 in normal and disease-associated osteogenic cells

Luca Dalle Carbonare1, Macarena Gomez Lira2, Arianna Minoia1

  • 1Department of Medicine, University of Verona, Verona, Italy.

Insights

FBXW11 (b-TrCP2) expression changes during bone cell development and is elevated in mesenchymal stem cells and cleidocranial dysplasia patients, impacting cellular proliferation and homeostasis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The ubiquitin-proteasome system (UPS) is crucial for cellular homeostasis through protein degradation.
  • FBXW11 (b-TrCP2) is an F-box protein that targets proteins for UPS degradation, influencing cell cycle and proliferation.
  • FBXW11's role in osteogenic cells remains largely unexplored despite its known involvement in embryogenesis and cancer.

Purpose of the Study:

  • To investigate FBXW11 gene expression modulation within the osteogenic lineage.
  • To analyze FBXW11 expression in normal and pathological osteogenic conditions, including mesenchymal stem cells (MSCs), cleidocranial dysplasia (CCD), and osteosarcoma.

Main Methods:

  • In vitro and ex vivo molecular investigations were conducted.
  • FBXW11 expression was analyzed in normal osteogenic cells, MSCs, and cells from CCD patients and osteosarcoma.
  • Post-transcriptional regulation of FBXW11 and its effect on beta-catenin levels were examined in osteosarcoma cells.

Main Results:

  • FBXW11 expression is modulated during osteogenesis.
  • FBXW11 is overexpressed in circulating MSCs and in osteogenically stimulated cells from CCD patients.
  • FBXW11 undergoes post-transcriptional regulation in osteosarcoma cells, leading to elevated beta-catenin levels.

Conclusions:

  • FBXW11 expression is dynamically regulated throughout the osteogenic lineage.
  • Dysregulation of FBXW11 is observed in impaired osteogenic cells, such as those from CCD patients and osteosarcoma.
  • FBXW11 plays a significant role in osteogenesis and its aberrant expression contributes to pathological conditions.

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