Ganoderal A effectively induces the osteogenic differentiation of human amniotic mesenchymal stem cells via Wnt/β-catenin and BMPs/SMADs signaling pathways.
Ganoderal A effectively induces the osteogenic differentiation of human amniotic mesenchymal stem cells via Wnt/β-catenin and BMPs/SMADs signaling pathways.
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Ganoderal A 通过 Wnt/β-catenin 和 BMPs/SMADs 信号通路有效诱导人羊膜间充质干细胞的成骨分化。
DOI：
10.1016/j.biopha.2019.109807
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发表时间：
2020
影响因子：
7.5
通讯作者：
Xiao Jian-Hui
中科院分区：
文献类型：
--
作者：
Wang Yi-Qing;Wang Nuo-Xin;Luo Yi;Yu Chang-Yin;Xiao Jian-Hui
成骨诱导剂在有效的基于干细胞的骨缺损/丢失治疗中发挥核心作用。然而，目前常规的成骨诱导剂是由三种成分组成的鸡尾酒，由于诱导效率低和副作用，必须加以改进。因此，迫切需要开发更安全、更有效的骨诱导剂。本实验研究了灵芝素A（GanoderalA，GD-A）的成骨作用。GD-A在0.001-10 μM剂量下对人羊膜间充质干细胞（hAMSC）无细胞毒性;此外，0.01 μM GD-A显著诱导hAMSC中成骨细胞特异性标志物（如碱性磷酸酶）和钙沉积的产生。在分子水平上，GD-A促进多种成骨细胞分化标志物的表达，如RUNX 2、OSX、OPN、ALP、OCN和COL 1 α1。Wnt/β-catenin和BMP/SMAD信号在hAMSC骨分化过程中显示出活性。此外，KYA 1797 K和SB 431542单独或联合使用时，特异性阻断这两种信号可显著抑制碱性磷酸酶分泌以及RUNX 2和ALP表达。与此同时，两个信号也都被屏蔽了。这些发现表明，GD-A通过Wnt/β-catenin和BMP/SMAD之间的信号串扰诱导hAMSC分化为成骨细胞。总之，GD-A是一种安全、有效和新型的骨诱导剂，可用于基于干细胞的骨缺损/丢失治疗。
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 fromGanoderma 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 asRUNX2, OSX, OPN, ALP, OCN, andCOL1α1. 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 andRUNX2andALPexpression 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.