Astragaloside‑IV modulates NGF‑induced osteoblast differentiation via the GSK3β/β‑catenin signalling pathway

Mol Med Rep. 2021 Jan;23(1):19. doi: 10.3892/mmr.2020.11657. Epub 2020 Nov 12.

Abstract

Astragaloside (AST) is derived from the Chinese herb <em>Astragalus membranaceus</em>, and studies have demonstrated that it promotes differentiation of bone marrow‑derived mesenchymal stem cells (BMSCs). To the best of our knowledge, however, the functions of the component AST‑IV in osteogenesis have not previously been elucidated. The present study aimed to verify the effects of AST‑IV in osteogenesis. First, the proliferation and differentiation status of human BMSCs incubated with AST‑IV were analysed and compared with a control (no AST‑IV treatment). In order to determine the involvement of the glycogen synthase kinase (GSK)3β signalling pathway in AST‑IV, overexpression and inhibition of GSK3β was induced during incubation of BMSCs with AST‑IV. In order to investigate how neuronal growth factor (NGF) contributes to BMSCs differentiation, BMSCs were co‑incubated with an anti‑NGF antibody and AST IV, and then levels of osteogenesis markers were assessed. The results demonstrated for the first time that AST‑IV contributed to BMSCs differentiation. Furthermore, the GSK3β/β‑catenin signalling pathway was revealed to be involved in AST‑IV‑induced osteogenesis; moreover, AST‑IV accelerated differentiation by enhancing the expression levels of NGF. In summary, the present study demonstrated that AST‑IV promotes BMSCs differentiation, thus providing a potential target for the treatment of osteoporosis.

Keywords: astragaloside‑IV; osteogenesis; bone marrow‑derived mesenchymal stem cells; neuronal growth factor; lycogen synthase kinase 3β.

MeSH terms

  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Gene Expression Regulation / drug effects
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Humans
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • Nerve Growth Factor / metabolism
  • Osteogenesis*
  • Osteoporosis / drug therapy
  • Osteoporosis / metabolism*
  • Saponins / pharmacology*
  • Triterpenes / pharmacology*
  • Wnt Signaling Pathway / drug effects*

Substances

  • NGF protein, human
  • Saponins
  • Triterpenes
  • astragaloside A
  • Nerve Growth Factor
  • Glycogen Synthase Kinase 3 beta