<p>Recently, several drugs have been discovered that primarily function through direct action on cells within tissues or in combination with tissue-engineered scaffolds to promote the regenerative repair of bone tissue defects. Astragaloside&#xa0;IV&#xa0;(AS-IV), one of the main active ingredients in the Chinese herbal Astragalus film, exhibits anti-inflammatory, antioxidant, and vasoprotective pharmacological activities. Therefore, we hypothesized that AS-IV may induce the proliferation and osteogenic differentiation of human jaw bone marrow mesenchymal stem cells (hJBMMSCs), which is key to its potential application in the regeneration and repair of oral and maxillofacial bone tissue defects. This study aimed to investigate the effects of AS-IV&#xa0;on the proliferation and osteogenic differentiation of hJBMMSCs&#xa0;and the mechanisms involved. In this in vitro study, the cytotoxicity of AS-IV to hJBMMSCs was assessed&#xa0;using the CCK-8 assay. Osteogenic differentiation was evaluated via&#xa0;alkaline phosphatase&#xa0;(ALP)&#xa0;activity, calcium nodule formation, osteogenic and angiogenic gene expression, and osteogenic protein levels. In addition, the potential molecular mechanism underlying AS-IV-induced osteogenic differentiation of hJBMMSCs was preliminarily explored using LY294002, a specific PI3K/AKT antagonist. AS-IV significantly promoted the proliferation and osteogenic differentiation of hJBMMSCs at tested concentrations. Notably, treatment with 40&#xa0;µM&#xa0;AS-IV supplemented in differentiation medium significantly enhanced cell proliferation, migration, and mineral deposition. Reverse transcription quantitative PCR revealed that 40&#xa0;µM AS-IV&#xa0;increased the expression of osteogenic&#xa0;and angiogenic genes such as ALP, Runx2, OPN,&#xa0;OCN, CD31, VEGF, and Ang-1 in hJBMMSCs. Western blot analysis further showed that 40&#xa0;µM AS-IV&#xa0;upregulated the levels of the osteogenic proteins Runx-2 and OCN. These effects may be mediated by AS-IV through activation of the PI3K/AKT signaling pathway. Overall, AS-IV promotes hJBMMSC proliferation and osteogenic differentiation by activating the&#xa0;PI3K/AKT pathway and upregulating osteogenic and angiogenesis-related genes.</p>

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Effects of astragaloside IV on the proliferation and osteogenic differentiation of human jaw bone marrow mesenchymal stem cells in vitro

  • Zonghao Hu,
  • Zishun Qin,
  • Lihua Yin

摘要

Recently, several drugs have been discovered that primarily function through direct action on cells within tissues or in combination with tissue-engineered scaffolds to promote the regenerative repair of bone tissue defects. Astragaloside IV (AS-IV), one of the main active ingredients in the Chinese herbal Astragalus film, exhibits anti-inflammatory, antioxidant, and vasoprotective pharmacological activities. Therefore, we hypothesized that AS-IV may induce the proliferation and osteogenic differentiation of human jaw bone marrow mesenchymal stem cells (hJBMMSCs), which is key to its potential application in the regeneration and repair of oral and maxillofacial bone tissue defects. This study aimed to investigate the effects of AS-IV on the proliferation and osteogenic differentiation of hJBMMSCs and the mechanisms involved. In this in vitro study, the cytotoxicity of AS-IV to hJBMMSCs was assessed using the CCK-8 assay. Osteogenic differentiation was evaluated via alkaline phosphatase (ALP) activity, calcium nodule formation, osteogenic and angiogenic gene expression, and osteogenic protein levels. In addition, the potential molecular mechanism underlying AS-IV-induced osteogenic differentiation of hJBMMSCs was preliminarily explored using LY294002, a specific PI3K/AKT antagonist. AS-IV significantly promoted the proliferation and osteogenic differentiation of hJBMMSCs at tested concentrations. Notably, treatment with 40 µM AS-IV supplemented in differentiation medium significantly enhanced cell proliferation, migration, and mineral deposition. Reverse transcription quantitative PCR revealed that 40 µM AS-IV increased the expression of osteogenic and angiogenic genes such as ALP, Runx2, OPN, OCN, CD31, VEGF, and Ang-1 in hJBMMSCs. Western blot analysis further showed that 40 µM AS-IV upregulated the levels of the osteogenic proteins Runx-2 and OCN. These effects may be mediated by AS-IV through activation of the PI3K/AKT signaling pathway. Overall, AS-IV promotes hJBMMSC proliferation and osteogenic differentiation by activating the PI3K/AKT pathway and upregulating osteogenic and angiogenesis-related genes.