The Korean journal of internal medicine

The Korean Association of Internal Medicine (대한내과학회)
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Atorvastatin inhibits osteoclast differentiation by suppressing NF-κB and MAPK signaling during IL-1β-induced osteoclastogenesis

  • Lee, Won-Seok (Division of Rheumatology, Department of Internal Medicine, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University- Biomedical Research Institute of Chonbuk National University Hospital) ;
  • Lee, Eun-Gyeong (Division of Rheumatology, Department of Internal Medicine, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University- Biomedical Research Institute of Chonbuk National University Hospital) ;
  • Sung, Myung-Soon (Division of Rheumatology, Department of Internal Medicine, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University- Biomedical Research Institute of Chonbuk National University Hospital) ;
  • Choi, Yun-Jung (Division of Rheumatology, Department of Internal Medicine, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University- Biomedical Research Institute of Chonbuk National University Hospital) ;
  • Yoo, Wan-Hee (Division of Rheumatology, Department of Internal Medicine, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University- Biomedical Research Institute of Chonbuk National University Hospital)
  • Received : 2015.07.28
  • Accepted : 2016.03.11
  • Published : 2018.03.01
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Abstract

Background/Aims: To define the effect of statins on interleukin $1{\beta}$ (IL-$1{\beta}$)-induced osteoclastogenesis and elucidate the underlying mechanisms. Methods: Bone marrow cells were obtained from 5-week-old male ICR (Institute for Cancer Research) mice, and they were cultured to differentiate them into osteoclasts with macrophage colony-stimulating factor and the receptor activator of nuclear factor (NF)-${\kappa}B$ ligand in the presence or absence of IL-$1{\beta}$ or atorvastatin. The formation of osteoclasts was evaluated by tartrate-resistant acid phosphatase (TRAP) staining and resorption pit assay with dentine slice. The molecular mechanisms of the effects of atorvastatin on osteoclastogenesis were investigated using reverse transcription polymerase chain reaction and immunoblotting for osteoclast specific molecules. Results: Atorvastatin significantly reduced the number of TRAP-positive multinucleated cells as well as the bone resorption area. Atorvastatin also downregulated the expression of the NF of activated T-cell c1 messenger RNA and inhibited the expression of osteoclast-specific genes. A possible underlying mechanism may be that atorvastatin suppresses the degradation of the inhibitors of NF-${\kappa}B$ and blocks the activation of the c-Jun N-terminal kinase, extracellular signal-regulated kinase, and p38; thus, implicating the NF-${\kappa}B$ and mitogen-activated protein kinases pathway in this process. Conclusions: Atorvastatin is a strong inhibitor of inflammation-induced osteoclastogenesis in inflammatory joint diseases.

Keywords

Acknowledgement

Supported by : Biomedical Research Institute, Chonbuk National University Hospital

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