Gentiopicroside promotes the osteogenesis of bone mesenchymal stem cells by modulation of β-catenin-BMP2 signalling pathway

Huaji Jiang, Jialiang Zhong, Wenjun Li, Jianghui Dong, Cory J. Xian, Yung Kang Shen, Lufeng Yao, Qiang Wu, Liping Wang

Research output: Contribution to journalArticlepeer-review

Abstract

Osteoporosis is characterized by increased bone fragility, and the drugs used at present to treat osteoporosis can cause adverse reactions. Gentiopicroside (GEN), a class of natural compounds with numerous biological activities such as anti-resorptive properties and protective effects against bone loss. Therefore, the aim of this work was to explore the effect of GEN on bone mesenchymal stem cells (BMSCs) osteogenesis for a potential osteoporosis therapy. In vitro, BMSCs were exposed to GEN at different doses for 2 weeks, whereas in vivo, ovariectomized osteoporosis was established in mice and the therapeutic effect of GEN was evaluated for 3 months. Our results in vitro showed that GEN promoted the activity of alkaline phosphatase, increased the calcified nodules in BMSCs and up-regulated the osteogenic factors (Runx2, OSX, OCN, OPN and BMP2). In vivo, GEN promoted the expression of Runx2, OCN and BMP2, increased the level of osteogenic parameters, and accelerated the osteogenesis of BMSCs by activating the BMP pathway and Wnt/β-catenin pathway, effect that was inhibited using the BMP inhibitor Noggin and Wnt/β-catenin inhibitor DKK1. Silencing the β-catenin gene and BMP2 gene blocked the osteogenic differentiation induced by GEN in BMSCs. This block was also observed when only β-catenin was silenced, although the knockout of BMP2 did not affect β-catenin expression induced by GEN. Therefore, GEN promotes BMSC osteogenesis by regulating β-catenin-BMP signalling, providing a novel strategy in the treatment of osteoporosis.

Original languageEnglish
Pages (from-to)10825-10836
Number of pages12
JournalJournal of Cellular and Molecular Medicine
Volume25
Issue number23
DOIs
Publication statusPublished - Dec 2021

Keywords

  • BMP pathway
  • Gentiopicroside
  • osteogenic factors
  • osteogenic parameters
  • osteoporosis
  • Wnt/β-catenin pathway

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

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