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Updated: Dec 1, 2025

Isolation of Mesenchymal Stem Cells from Human Alveolar Periosteum and Effects of Vitamin D on Osteogenic Activity of Periosteum-derived Cells
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Isolation of Mesenchymal Stem Cells from Human Alveolar Periosteum and Effects of Vitamin D on Osteogenic Activity of Periosteum-derived Cells

Published on: May 4, 2018

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1,25(OH)2D3 inhibits osteogenic differentiation through activating β‑catenin signaling via downregulating bone

Xiaofeng Han1, Naifeng Zhu1, Yihan Wang1

  • 1Department of Orthopedics, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China.

Molecular Medicine Reports
|November 11, 2020
PubMed

Insights

1,25(OH)2D3 inhibits osteogenic differentiation in bone marrow-derived mesenchymal stem cells (BMSCs) by inactivating bone morphogenetic proteins (BMPs) and activating Wnt/β-catenin signaling. This study elucidates the molecular mechanisms underlying vitamin D

Area of Science:

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Background:

  • Osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) is crucial for bone formation.
  • 1,25(OH)2D3 is known to influence bone metabolism, but its precise effects on BMSC osteogenesis and underlying molecular pathways require further elucidation.

Purpose of the Study:

  • To investigate the involvement of bone morphogenetic proteins (BMPs) and Wnt/β-catenin signaling in 1,25(OH)2D3-induced inhibition of osteogenic differentiation in BMSCs.

Main Methods:

  • Assessed osteogenic differentiation markers (BMP2, Runx2, Msx2, OPN, OCN, ALP activity, Alizarin red-S staining).
  • Utilized Chromatin Immunoprecipitation (ChIP) for DNA methylation and histone modification analysis of the BMP2 promoter.
  • Employed Immunoprecipitation (IP) assays to examine protein interactions (Smad1 and Dvl-1).

Main Results:

  • 1,25(OH)2D3 significantly decreased osteogenic markers and calcified area, effects reversed by BMP2 overexpression.
  • 1,25(OH)2D3 increased H3K9me2 and decreased histone H3 acetylation at the BMP2 promoter.
  • 1,25(OH)2D3 promoted nuclear β-catenin accumulation by downregulating BMP2, and Wnt/β-catenin inhibition partially reversed the effects.

Conclusions:

  • 1,25(OH)2D3 inhibits BMSC osteogenic differentiation by inactivating BMP2 signaling and activating Wnt/β-catenin signaling.
  • Epigenetic modifications at the BMP2 promoter and crosstalk between BMP and Wnt pathways are key mechanisms involved.

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