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SAT0304 Atorvastatin Inhibits Osteoclast Differentiation and Bone Resorbing Activity by Suppressing NF-κB and Mapk Signaling During IL-1β-Induced Osteoclastogenesis
  1. W.S. Lee1,
  2. Y.J. Choi1,
  3. M.-J. Hong2,
  4. C.-H. Lee3,
  5. M.S. Lee3,
  6. S.-I. Lee4,
  7. W.-H. Yoo1
  1. 1Division of Rheumatology, Department of Internal Medicine, Chonbuk National University Medical School and Research Institute of Clinical Medicine of Chonbuk National University Hospital-Chonbuk National University
  2. 2Division of Rheumatology, Department of Internal Medicine, Presbyterian Medical center, jeonju
  3. 3Division of Rheumatology, Department of Internal Medicine, School of Medicine, Wonkwang university, Iksan
  4. 4Division of Rheumatology, Department of Internal Medicine, Gyeongsang National University School of Medicine, Jinju, Korea, Republic Of

Abstract

Background 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) are potent inhibitors of cholesterol biosynthesis. They have been reported to have anti-inflammatory and/or immunomodulatory as well as prophylactic and therapeutic effects in collagen-induced arthritis models. Bone erosion is a central feature of rheumatoid arthritis and is associated with disease severity and poor functional outcome.

Objectives This study was designed to define the effect of statins on IL-1β-induced osteoclastogenesis and to elucidate the underlying mechanisms.

Methods Bone marrow cells (BMCs) were obtained from 5-week-old male ICR mice and cultured to differentiate them into osteoclasts with M-CSF and RANKL in the presence or absence of IL-1β 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 above effects of atorvastatin on osteoclastogenesis were investigated using RT-PCR 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 NFATc1 mRNA and inhibited the expression of osteoclast-specific genes. A possible underlying mechanism may be that atorvastatin suppresses the degradation of the inhibitors of NF-κB and blocks the activation of c-JUN N-terminal kinase, extracellular signal-regulated kinase, and p38, thus implicating the NF-κB and MAPK pathway in this process.

Conclusions These results indicate that atorvastatin is a strong inhibitor of inflammation-induced osteoclastogenesis in inflammatory joint diseases

Disclosure of Interest None declared

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