Korean J Intern Med.  2018 Mar;33(2):397-406. 10.3904/kjim.2015.244.

Atorvastatin inhibits osteoclast differentiation by suppressing NF-κB and MAPK signaling during IL-1β-induced osteoclastogenesis

• Lee WS
• Lee EG
• Sung MS
• Choi YJ
• Yoo WH

• KMID: 2411552
• DOI: http://doi.org/10.3904/kjim.2015.244

Abstract

BACKGROUND/AIMS
To define the effect of statins on interleukin 1β (IL-1β)-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)-κB ligand 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 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-κB and blocks the activation of the c-Jun N-terminal kinase, extracellular signal-regulated kinase, and p38; thus, implicating the NF-κB and mitogen-activated protein kinases pathway in this process.
CONCLUSIONS
Atorvastatin is a strong inhibitor of inflammation-induced osteoclastogenesis in inflammatory joint diseases.

Keyword

Atorvastatin; Joint diseases; Osteoprotegerin; Mice

MeSH Terms

Acid Phosphatase
Animals
Atorvastatin Calcium*
Bone Marrow Cells
Bone Resorption
Dentin
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Immunoblotting
Interleukins
JNK Mitogen-Activated Protein Kinases
Joint Diseases
Macrophage Colony-Stimulating Factor
Male
Mice
Mitogen-Activated Protein Kinases
Osteoclasts*
Osteoprotegerin
Phosphotransferases
Polymerase Chain Reaction
Reverse Transcription
RNA, Messenger
T-Lymphocytes
Acid Phosphatase
Atorvastatin Calcium
Interleukins
JNK Mitogen-Activated Protein Kinases
Macrophage Colony-Stimulating Factor
Mitogen-Activated Protein Kinases
Osteoprotegerin
Phosphotransferases
RNA, Messenger