Aster saponin A2 inhibits osteoclastogenesis through mitogen-activated protein kinase-c-Fos-NFATc1 signaling pathway

J Vet Sci. 2022 Jul;23(4):e47. doi: 10.4142/jvs.21246. Epub 2022 Apr 11.

Abstract

Background: In lipopolysaccharide-induced RAW264.7 cells, Aster tataricus (AT) inhibits the nuclear factor kappa-light-chain-enhancer of activated B cells and MAPKs pathways and critical pathways of osteoclast development and bone resorption.

Objectives: This study examined how aster saponin A2 (AS-A2) isolated from AT affects the processes and function of osteoclastogenesis induced by receptor activator of nuclear factor kappa-B ligand (RANKL) in RAW264.7 cells and bone marrow macrophages (BMMs).

Methods: The cell viability, tartrate-resistant acid phosphatase staining, pit formation assay, polymerase chain reaction, and western blot were carried out to determine the effects of AS-A2 on osteoclastogenesis.

Results: In RAW264.7 and BMMs, AS-A2 decreased RANKL-initiated osteoclast differentiation in a concentration-dependent manner. In AS-A2-treated cells, the phosphorylation of ERK1/2, JNK, and p38 protein expression were reduced considerably compared to the control cells. In RAW264.7 cells, AS-A2 suppressed the RANKL-induced activation of osteoclast-related genes. During osteoclast differentiation, AS-A2 suppressed the transcriptional and translational expression of NFATc1 and c-Fos. AS-A2 inhibited osteoclast development, reducing the size of the bone resorption pit area.

Conclusion: AS-A2 isolated from AT appears to be a viable therapeutic therapy for osteolytic illnesses, such as osteoporosis, Paget's disease, and osteogenesis imperfecta.

Keywords: RANK ligand; Saponins; macrophage colony-stimulating factor; osteoclasts; tartrate-resistant acid phosphatase.

MeSH terms

  • Animals
  • Bone Marrow Cells / metabolism
  • Bone Resorption* / genetics
  • Bone Resorption* / metabolism
  • Bone Resorption* / veterinary
  • Cell Differentiation
  • Mitogen-Activated Protein Kinases / metabolism
  • Mitogen-Activated Protein Kinases / pharmacology
  • Mitogens / metabolism
  • Mitogens / pharmacology
  • NF-kappa B / metabolism
  • NFATC Transcription Factors / genetics
  • NFATC Transcription Factors / metabolism
  • NFATC Transcription Factors / pharmacology
  • Osteoclasts / metabolism
  • Osteogenesis / physiology
  • RANK Ligand / metabolism
  • RANK Ligand / pharmacology
  • Saponins* / pharmacology
  • Signal Transduction

Substances

  • Mitogens
  • NF-kappa B
  • NFATC Transcription Factors
  • RANK Ligand
  • Saponins
  • Mitogen-Activated Protein Kinases