Astragalus polysaccharide attenuates LPS-related inflammatory osteolysis by suppressing osteoclastogenesis by reducing the MAPK signalling pathway

J Cell Mol Med. 2021 Jul;25(14):6800-6814. doi: 10.1111/jcmm.16683. Epub 2021 Jun 2.

Abstract

Bacterial products can stimulate inflammatory reaction and activate immune cells to enhance the production of inflammatory cytokines, and finally promote osteoclasts recruitment and activity, leading to bone destruction. Unfortunately, effective preventive and treatment measures for inflammatory osteolysis are limited and usually confuse the orthopedist. Astragalus polysaccharide (APS), the main extractive of Astragali Radix, has been widely used for treating inflammatory diseases. In the current study, in vitro and in vivo experimental results demonstrated that APS notably inhibited osteoclast formation and differentiation dose-dependently. Moreover, we found that APS down-regulated RANKL-related osteoclastogenesis and levels of osteoclast marker genes, such as NFATC1, TRAP, c-FOS and cathepsin K. Further underlying mechanism investigation revealed that APS attenuated activity of MAPK signalling pathways (eg ERK, JNK and p38) and ROS production induced by RANKL. Additionally, APS was also found to suppress LPS-related inflammatory osteolysis by decreasing inflammatory factors' production in vivo. Overall, our findings demonstrate that APS effectively down-regulates inflammatory osteolysis due to osteoclast differentiation and has the potential to become an effective treatment of the disorders associated with osteoclast.

Keywords: Astragalus polysaccharide; inflammatory osteolysis; lipopolysaccharide; osteoclastogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Astragalus Plant / chemistry*
  • Cathepsin K / metabolism
  • Cells, Cultured
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Lipopolysaccharides / toxicity
  • MAP Kinase Signaling System*
  • Mice
  • Mice, Inbred C57BL
  • NFATC Transcription Factors / metabolism
  • Osteoclasts / drug effects
  • Osteoclasts / metabolism*
  • Osteogenesis*
  • Osteolysis / drug therapy*
  • Osteolysis / etiology
  • Osteolysis / metabolism
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use*
  • Polysaccharides / pharmacology
  • Polysaccharides / therapeutic use
  • Proto-Oncogene Proteins c-fos / metabolism
  • RANK Ligand / metabolism
  • RAW 264.7 Cells
  • Reactive Oxygen Species / metabolism
  • Tartrate-Resistant Acid Phosphatase / metabolism
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Anti-Inflammatory Agents
  • Lipopolysaccharides
  • NFATC Transcription Factors
  • Nfatc1 protein, mouse
  • Plant Extracts
  • Polysaccharides
  • Proto-Oncogene Proteins c-fos
  • RANK Ligand
  • Reactive Oxygen Species
  • Tnfsf11 protein, mouse
  • Extracellular Signal-Regulated MAP Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Acp5 protein, mouse
  • Tartrate-Resistant Acid Phosphatase
  • Cathepsin K