Rosiglitazone inhibition of calvaria-derived osteoblast differentiation is through both of PPARγ and GPR40 and GSK3β-dependent pathway

Mol Cell Endocrinol. 2015 Sep 15:413:78-89. doi: 10.1016/j.mce.2015.06.013. Epub 2015 Jun 24.

Abstract

Rosiglitazone (RSG) can cause bone loss, however the mechanisms remain largely unknown. This study aims to investigate the effects of RSG on differentiation and mineralization of osteoblasts using primary cultured mouse fetal calvaria-derived osteoblasts as a model, and elucidate the receptor and signaling pathways responsible for these effects. We found that RSG suppressed the differentiation and mineralization of calvaria-derived osteoblasts. Peroxisome proliferators-activated receptor γ (PPARγ) siRNA significantly reversed the inhibitory effect of RSG on osteogenic differentiation. The expression of G protein-coupled receptor (GPR) 40 was suppressed during differentiation, but was increased by RSG treatment. GPR40 siRNA significantly reversed the inhibitory effect of RSG on osteogenesis. RSG activated glycogen synthase kinase (GSK)-3β, which in turn decreased β-catenin expression. RSG-induced GSK3β activation was mediated through both PPARγ and GPR40. These results suggest that both PPARγ and GRP40 are required for RSG-induced inhibition of mouse calvaria osteoblast differentiation, which is mediated through GSK3β-dependent pathway.

Keywords: GPR40; GSK3β; Osteoblast; PPARγ; Rosiglitazone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / physiology*
  • Glycogen Synthase Kinase 3 / metabolism*
  • Glycogen Synthase Kinase 3 beta
  • Mice
  • Osteoblasts / cytology
  • Osteoblasts / metabolism*
  • Osteogenesis / physiology
  • PPAR gamma / metabolism*
  • Receptors, G-Protein-Coupled / metabolism*
  • Signal Transduction / physiology*
  • Skull / cytology
  • Skull / metabolism*

Substances

  • Ffar1 protein, mouse
  • PPAR gamma
  • Receptors, G-Protein-Coupled
  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, mouse
  • Glycogen Synthase Kinase 3