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

  • Su, Xiang-Dong (School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University) ;
  • Yang, Seo Y (Department of Pharmaceutical Engineering, Sangji University) ;
  • Shrestha, Saroj K (Department of Dental Pharmacology, School of Dentistry, Jeonbuk National University) ;
  • Soh, Yunjo (Department of Dental Pharmacology, School of Dentistry, Jeonbuk National University)
  • Received : 2021.09.23
  • Accepted : 2022.03.10
  • Published : 2022.07.31

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

Acknowledgement

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education (NRF-2021R1I1A3055927 to Soh Y), Research Base Construction Fund Support Program funded by Jeonbuk National University in 2021 (Soh Y) and the Ministry of Education, Science and Technology (NRF-2018R1A6A3A11047338 to Yang SY).

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