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Marein Prevented LPS-Induced Osteoclastogenesis by Regulating the NF-κB Pathway In Vitro

  • Li, Yuling (Department of Orthopaedics, Affiliated Hospital of North Sichuan Medical College) ;
  • Zhang, Jing (Department of Gastroenterology, Affiliated Hospital of North Sichuan Medical College) ;
  • Yan, Caiping (Department of Orthopaedics, Affiliated Hospital of North Sichuan Medical College) ;
  • Chen, Qian (Department of Orthopaedics, Affiliated Hospital of North Sichuan Medical College) ;
  • Xiang, Chao (Department of Orthopaedics, Affiliated Hospital of North Sichuan Medical College) ;
  • Zhang, Qingyan (Department of Orthopaedics, Affiliated Hospital of North Sichuan Medical College) ;
  • Wang, Xingkuan (Department of Orthopaedics, Affiliated Hospital of North Sichuan Medical College) ;
  • Jiang, Ke (Department of Orthopaedics, Affiliated Hospital of North Sichuan Medical College)
  • Received : 2021.09.16
  • Accepted : 2022.01.10
  • Published : 2022.02.28

Abstract

Many bone diseases such as osteolysis, osteomyelitis, and septic arthritis are caused by gram-negative bacterial infection, and lipopolysaccharide (LPS), a bacterial product, plays an essential role in this process. Drugs that inhibit LPS-induced osteoclastogenesis are urgently needed to prevent bone destruction in infective bone diseases. Marein, a major bioactive compound of Coreopsis tinctoria, possesses anti-oxidative, anti-inflammatory, anti-hypertensive, anti-hyperlipidemic, and anti-diabetic effects. In this study, we measured the effect of marein on RAW264.7 cells by CCK-8 assay and used TRAP staining to determine osteoclastogenesis. The levels of osteoclast-related genes and NF-κB-related proteins were then analyzed by western blot, and the levels of pro-inflammatory cytokines were quantified by ELISA. Our results showed that marein inhibited LPS-induced osteoclast formation by osteoclast precursor RAW264.7 cells. The effect of marein was related to its inhibitory function on expressions of pro-inflammatory cytokines and osteoclast-related genes containing RANK, TRAF6, MMP-9, CK, and CAII. Additionally, marein leads to markedly inhibited NF-κB signaling pathway activation in LPS-induced RAW264.7 cells. Concurrently, when the NF-κB signaling pathway was inhibited, osteoclast formation and pro-inflammatory cytokine expression were decreased. Collectively, marein could inhibit LPS-induced osteoclast formation in RAW264.7 cells via regulating the NF-κB signaling pathway. Our data demonstrate that marein might be a potential drug for bacteria-induced bone destruction disease. Our findings provide new insights into LPS-induced bone disease.

Keywords

Acknowledgement

This study was supported by the Foundation for Young Scientist of the Medical Association of Sichuan Province (Q19069), the Research Foundation of Science and Technology Bureau of Nanchong City (18SXHZ0147), Major Program of Science Foundation of Affiliated Hospital of North Sichuan Medical College (2019ZD008), the Research Project of the Affiliated Hospital of North Sichuan Medical College (2021ZK001), the Applied Basic Research Programs of the Science and Technology Department of Sichuan Province (2021YJ0467), and the National Natural Science Foundation of China (82102578).

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