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

Aster saponin A ₂ inhibits osteoclastogenesis through mitogenactivated protein kinase-c-Fos-NFATc1 signaling pathway

• Su XD
• Yang SY
• Shrestha SK
• Soh Y

• KMID: 2532281
• DOI: http://doi.org/10.4142/jvs.21246

Abstract

Background
In lipopolysaccharide-induced RAW264.7 cells, Aster tartaric (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 ASA2 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.

Keyword

Saponins; osteoclasts; tartrate-resistant acid phosphatase; macrophage colonystimulating factor; RANK ligand