1. Academic Validation
  2. Ganoderal A effectively induces osteogenic differentiation of human amniotic mesenchymal stem cells via cross-talk between Wnt/β-catenin and BMP/SMAD signaling pathways

Ganoderal A effectively induces osteogenic differentiation of human amniotic mesenchymal stem cells via cross-talk between Wnt/β-catenin and BMP/SMAD signaling pathways

  • Biomed Pharmacother. 2020 Mar;123:109807. doi: 10.1016/j.biopha.2019.109807.
Yi-Qing Wang 1 Nuo-Xin Wang 2 Yi Luo 2 Chang-Yin Yu 3 Jian-Hui Xiao 4
Affiliations

Affiliations

  • 1 Zunyi Municiptal Key Laboratory of Medicinal Biotechnology, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, China.
  • 2 Zunyi Municiptal Key Laboratory of Medicinal Biotechnology, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, China; Center for Translational Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, China.
  • 3 Department of Neurology, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, China. Electronic address: yuchangyin68@163.com.
  • 4 Zunyi Municiptal Key Laboratory of Medicinal Biotechnology, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, China; Center for Translational Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, China. Electronic address: jhxiao@zmu.edu.cn.
Abstract

Osteogenic inducers play central roles in effective stem cell-based treatment of bone defects/losses. However, the current routine osteogenic inducer is a cocktail comprising three components that must be improved due to low induction efficiency and side effects. Therefore, there is an urgent need to develop safer and more effective osteoinducers. Herein, we demonstrated the osteogenic effect of Ganoderal A (GD-A), a tetracyclic triterpenoid compound from Ganoderma lucidum. GD-A showed no cytotoxicity toward human amniotic mesenchymal stem cells (hAMSCs) at doses of 0.001-10 μM; furthermore, 0.01 μM GD-A significantly induced the generation of osteoblast-specific markers, such as Alkaline Phosphatase, and calcium deposition in hAMSCs. At molecular levels, GD-A promoted the expression of multiple osteoblast differentiation markers, such as RUNX2, OSX, OPN, ALP, OCN, and COL1α1. Both Wnt/β-catenin and BMP/SMAD signaling were shown as active during hAMSC osteodifferentiation. Furthermore, specific blocking of both signals by KYA1797K and SB431542 significantly inhibited Alkaline Phosphatase secretion and RUNX2 and ALP expression when used alone or in combination. Meanwhile, both signals were also blocked. These findings suggest that GD-A induces hAMSC differentiation into osteoblasts through signaling cross-talk between Wnt/β-catenin and BMP/SMAD. Taken together, GD-A is a safe, effective, and novel osteoinducer and might be used for stem cell-based therapy for bone defects/losses.

Keywords

BMP/SMAD signaling; Ganoderal A; Human amniotic mesenchymal stem cell; Osteogenic differentiation; Wnt/β-catenin signaling.

Figures
Products