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Tax1 binding protein 3 regulates osteogenic and adipogenic differentiation through inactivating Wnt/β-catenin

Yi Wang1, Ying Gan1, Yuan Dong2

  • 1NHC Key Lab of Hormones and Development, Tianjin Key Lab of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Institute of Endocrinology, Tianjin Medical University, Tianjin, China.

Journal of Cellular and Molecular Medicine
|March 9, 2023
PubMed

Insights

Tax1 binding protein 3 (Tax1bp3) regulates mesenchymal stem cell differentiation. This study shows Tax1bp3 inhibits osteogenesis while promoting adipogenesis by inactivating Wnt/β-catenin and BMP/Smads signaling.

Area of Science:

  • Cell Biology
  • Stem Cell Differentiation
  • Molecular Biology

Background:

  • Tax1 binding protein 3 (Tax1bp3) is a PDZ domain protein overexpressed in cancer.
  • Previous research identified Tax1bp3 as a β-catenin inhibitor.
  • The role of Tax1bp3 in mesenchymal progenitor cell differentiation was previously unknown.

Purpose of the Study:

  • To investigate the role of Tax1bp3 in osteogenic and adipogenic differentiation of mesenchymal progenitor cells.
  • To elucidate the molecular mechanisms underlying Tax1bp3's function in cell differentiation.

Main Methods:

  • Analysis of Tax1bp3 expression during osteoblast and adipocyte differentiation.
  • Overexpression and knockdown studies of Tax1bp3 in progenitor cells.
  • Ex vivo experiments using primary calvarial osteoblasts from knock-in mice.
  • Investigation of Wnt/β-catenin and BMP/Smads signaling pathways.

Main Results:

  • Tax1bp3 expression increased during induced osteogenic and adipogenic differentiation.
  • Overexpression of Tax1bp3 inhibited osteogenic differentiation and stimulated adipogenic differentiation.
  • Knockdown of Tax1bp3 yielded opposite effects on differentiation.
  • Tax1bp3 was found to inhibit both Wnt/β-catenin and BMP/Smads signaling pathways.

Conclusions:

  • Tax1bp3 reciprocally regulates osteogenic and adipogenic differentiation of mesenchymal progenitor cells.
  • Tax1bp3 inactivates Wnt/β-catenin and BMPs/Smads signaling pathways.
  • Inhibition of Wnt/β-catenin signaling is implicated in the reciprocal differentiation role of Tax1bp3.
Keywords:
SmadsTax1bp3adipocytebone morphogenetic proteinsdifferentiationosteoblastβ-catenin

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