Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
Atorvastatin and Simvastatin Inhibit Osteoclastogenesis by Decreasing the Expression of Receptor Activator of Nuclear Factor B Ligand (RANKL) in Rheumatoid Arthritis Fibroblast-Like Synoviocyte
Kim, Jeong Yeon, Lee, Eun Young, Lee, Eun Bong, Lee, Yun Jong, Hong, Yoo Jin, Park, Ji Ah, Yoo, Hyun Jung
To determine the effects and their mechanism of simvastatin and atorvastatin on the expression of osteoprotegerin (OPG) and receptor activator of nuclear factor k B ligand (RANKL) in RA fibroblast-like synoviocyte (FLS) and whether they inhibit osteoclastogenesis.
FLS was isolated from 3 RA patients and cultured in the presence of 20 ng/ml of TNF-a with or without atorvastatin or simvastatin for 24 hours. RANKL expression was assayed by Western blotting and reverse transcription-polymerase chain reaction (RT-PCR). OPG expression was measured by enzyme-linked immunosorbent assay and RT-PCR. Mevalonate was added to reverse the effect of atorvastatin and simvastatin on RA FLS. Phosphorylation of mitogen-activated protein kinases (MAPKs) [p38, Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERKs)] and Akt was detected by Western blotting. Peripheral blood mononuclear cells (PBMC) and RA FLS were cocultured in the presence of macrophage colony stimulating factor, 1,25-dihydroxyvitamin D3, and various concentrations of atorvastatin. Osteoclast formation was assayed by counting cells after staining for tartrate-resistant acid phosphatase.
Both atorvastain and simvastatin inhibited the expression of RANKL in RA FLS in a dose dependent manner, and the suppression of RANKL was reversed by mevalonate. Atorvastatin and simvastatin did not affect the OPG expression in RA FLS. Atorvastatin suppressed TNF-a induced p38 phosphorylation in RA FLS and also significantly decreased TRAP-positive multinucleated osteoclast formation in the coculture of PBMC and RA FLS.
Both atorvastatin and simvastatin suppressed RANKL expression in RA FLS. Atorvastatin inhibited osteoclast formation in the coculture of PBMC and RA FLS. These results suggest that atorvastatin and simvastatin may inhibit osteoclastogenesis and bone destruction in RA patients.
To cite this abstract, please use the following information:
Kim, Jeong Yeon, Lee, Eun Young, Lee, Eun Bong, Lee, Yun Jong, Hong, Yoo Jin, Park, Ji Ah, et al; Atorvastatin and Simvastatin Inhibit Osteoclastogenesis by Decreasing the Expression of Receptor Activator of Nuclear Factor B Ligand (RANKL) in Rheumatoid Arthritis Fibroblast-Like Synoviocyte [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1651