Purple tea water extract blocks RANKL-induced osteoclastogenesis through modulation of Akt/GSK3β and Blimp1-Irf8 pathways

Food Funct. 2022 Aug 30;13(17):8850-8859. doi: 10.1039/d2fo00780k.

Abstract

A number of studies demonstrated that some tea extracts exert inhibitory effects on osteoclastogenesis induced by receptor activator of nuclear factor κB ligand (RANKL). However, the effect of purple tea, a famous tea in China, on osteoclastogenesis remains unclear. In this study, a water-based purple tea extract (PTE) was found to suppress osteoclast formation, osteoclastic resorption pit area formation, and F-actin ring formation within RANKL-stimulated bone marrow macrophages (BMMs). Furthermore, our results demonstrated that PTE could inhibit expression of master transcription factors NFATc1 and c-Fos and their target genes DC-STAMP, Ctsk, and Atp6v0d2. Western blot analysis revealed that PTE treatment led to reduced RANKL-induced phosphorylation of Akt and GSK3β without altering transient activation of NF-κB and MAPKs (p38, JNK, ERK1/2) signaling. In addition, the results demonstrated that PTE treatment of RANKL-stimulated BMMs could down-regulate Blimp1 expression and up-regulate Irf8 expression. In summary, these results suggest that PTE treatment of RANKL-stimulated BMMs inhibited osteoclast differentiation via modulation of Blimp1-Irf8 and Akt/GSK3β signaling pathways. Aligning with our in vitro results, in vivo PTE administration ameliorated bone loss in LPS-treated mice. Taken together, the results presented in this work suggest that PTE treatment possesses anti-osteolytic activity.

MeSH terms

  • Animals
  • Bone Resorption* / drug therapy
  • Bone Resorption* / genetics
  • Bone Resorption* / metabolism
  • Cell Differentiation
  • Glycogen Synthase Kinase 3 beta / genetics
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Mice
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • NFATC Transcription Factors / genetics
  • NFATC Transcription Factors / metabolism
  • Osteoclasts
  • Osteogenesis
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • RANK Ligand* / metabolism
  • Tea / metabolism
  • Water / metabolism

Substances

  • NF-kappa B
  • NFATC Transcription Factors
  • RANK Ligand
  • Tea
  • Water
  • Glycogen Synthase Kinase 3 beta
  • Proto-Oncogene Proteins c-akt