Atorvastatin inhibit osteoclastogenesis by decreasing the expression of RANKL in the synoviocytes of rheumatoid arthritis Full Text
Arthritis Research & Therapy, 08/20/2012
Kim JY et al. – The results suggest that atorvastatin inhibits osteoclastogenesis and bone destruction in rheumatoid arthritis patients.Methods
- FLSs isolated from five RA patients were cultured in the presence of 20 ng/ml of TNF–alpha with or without atorvastatin.
- RANKL expressions were assayed by Western blotting and enzyme–linked immunosorbent assay.
- RANKL, RANK and OPG expression were assayed by reverse transcription–polymerase chain reaction (RT–PCR).
- Osteoclast formation was assayed by counting cells after staining for tartrate–resistant acid phosphatase in cocultures of peripheral blood mononuclear cells (PBMCs) and RA FLSs.
- Atorvastatin inhibited the expression of RANKL in RA FLSs in a dose–dependent manner, and the suppression of RANKL was prevented by mevalonate.
- However, OPG expression was not affected by atorvastatin in RA FLSs, and atorvastatin did not affect RANK expression in CD14+ cells.
- On the other hand, atorvastatin suppressed TNF–alpha induced p38 phosphorylation in RA FLSs and significantly reduced TRAP–positive multinucleated osteoclast formation in the coculture of PBMCs and RA FLSs.