S-Space College of Medicine/School of Medicine (의과대학/대학원) Dept. of Medicine (의학과) Theses (Master's Degree_의학과)
Atorvastatin inhibits osteoclastogenesis by decreasing the expression of receptor activator of nuclear factor κB ligand (RANKL) in the synoviocytes of rheumatoid arthritis
- 의과대학 의학과
- Issue Date
- 서울대학교 대학원
- 학위논문 (석사)-- 서울대학교 대학원 : 의학과, 2014. 2. 송영욱.
- Introduction: Statins, hydroxymethylglutaryl-coenzyme A reductase inhibitors, have been reported to have anti-inflammatory and/or immunomodulatory effects, and prophylactic and therapeutic effects in collagen induced arthritis -an experimental model of rheumatoid arthritis (RA). Here, the authors undertook to determine the effect of atorvastatin on the expressions of osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) in RA fibroblast-like synoviocytes (RA-FLSs), to identify the mechanisms responsible for these effects, and to determine whether the statin inhibit osteoclastogenesis.
Methods: FLSs isolated from five RA patients were cultured in the presence of 20 ng/ml of TNF-α 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.
Results: 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-α induced p38 phosphorylation in RA-FLSs and significantly reduced TRAP-positive multinucleated osteoclast formation in the coculture of PBMCs and RA-FLSs.
Conclusion: These results suggest that atorvastatin inhibits osteoclastogenesis and bone destruction in RA patients.