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The PPAR-γ/SFRP5/Wnt/β-catenin signal axis regulates the dexamethasone-induced osteoporosis

Hai-Peng He1, Shan Gu1

  • 1Shenzhen Institute of ENT & Longgang ENT Hospital, Shenzhen 518172, China.

Cytokine
|April 5, 2021
PubMed
Abstract

Insights

Glucocorticoids (GC) inhibit bone formation by affecting osteoblastic differentiation. This study shows that peroxisome proliferator-activated receptor-gamma (PPAR-γ) plays a key role in this process, impacting the Wnt/β-catenin pathway.

Area of Science:

  • Cell Biology
  • Stem Cell Research
  • Endocrinology

Background:

  • Glucocorticoids (GC) inhibit bone formation by suppressing osteoblastic differentiation of bone marrow stromal stem cells (BMSC).
  • Peroxisome proliferator-activated receptor-gamma (PPAR-γ) has been implicated in GC-mediated cellular processes.
  • The precise role of PPAR-γ in GC-induced inhibition of osteoblastogenesis remains to be fully elucidated.

Purpose of the Study:

  • To investigate the role of PPAR-γ in regulating osteoblastic differentiation of rat bone marrow stromal stem cells (rBMSC) under glucocorticoid treatment.
  • To explore the molecular mechanisms underlying PPAR-γ's influence on GC-induced suppression of osteogenesis.

Main Methods:

  • Established an in vitro model of GC-induced osteoporosis using dexamethasone (Dex)-treated rBMSC.
  • Quantified the expression of PPAR-γ, RUNX2, ALP, OPN, and SFRP5 using RT-qPCR and Western blot.
  • Assessed osteogenic differentiation via Alizarin Red S staining and manipulated PPAR-γ and SFRP5 levels using lentiviral vectors.

Main Results:

  • Dexamethasone significantly inhibited rBMSC osteoblastic differentiation and increased PPAR-γ expression.
  • Downregulation of PPAR-γ ameliorated the inhibitory effects of Dex on osteogenesis and promoted key osteogenic markers.
  • PPAR-γ knockdown led to decreased SFRP5 and increased Wnt/β-catenin signaling, which was reversed by SFRP5 overexpression.

Conclusions:

  • PPAR-γ plays a critical role in mediating the inhibitory effects of glucocorticoids on osteoblastic differentiation.
  • The PPAR-γ/SFRP5 axis regulates osteogenic differentiation through the Wnt/β-catenin signaling pathway in the context of GC-induced osteoporosis.
Keywords:
Osteoblastic differentiationPPAR-γSFRP5Wnt/β-catenin signaling pathway

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