| Lipoic Acid Directly Suppresses Osteclastogenesis and Bone Resorption |
| 알파 리포산에 의한 파골세포 형성 및 골흡수의 억제 |
| 김하영,고정민1,이영선2,김덕재1,김기수1 |
| 원광대학교 의과대학 산본병원 내과학교실, 울산대학교 의과대학 서울아산병원 내과학교실1,
아산생명과학 연구소2
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| Abstract |
Background
α-Lipoic acid (α-LA), a thiol antioxidant, suppressed TNF-α-induced apoptosis of human bone marrow stromal cells (hBMSC) in our previous study, suggesting that α-LA may stimulate bone formation. In the present study, we examined effects of α-LA on protein secretions into hBMSC culture media in order to investigate whether α-LA can modulate cell-to-cell interactions, and noted that α-LA stimulated secreted receptor activator of NF-κB ligand (RANKL). Therefore, we examined the effect of α-LA on osteoclastogenesis and bone resorption.
Method: After incubation of HS-5 cells with or without α-LA, we performed 2-dimensional electrophoresis and MALDI-TOF analysis. RANKL and osteoprotegerin levels were determined by ELISA assay. Tartrate-resistant acid phosphatase (TRAP) staining was performed in order to evaluate osteoclastogenesis, both in a coculture system of mouse bone marrow cells and osteoblasts, and in a mouse bone marrow cell culture system. Bone resorption was evaluated using dentine slices.
Results
Using proteomic analysis, we identified six differentially expressed proteins in the conditioned media of α-LA-treated hBMSC. One of these proteins, RANKL was significantly up regulated, as confirmed by immunoblotting with anti-RANKL antibody. ELISA assay showed that α-LA stimulated RANKL production in cellular extracts (membranous RANKL) about 5-fold and in conditioned media (soluble RANKL) about 23-fold, but had no effect on osteoprotegerin secretion. Despite increasing the RANKL/OPG ratio, α-LA showed a dose-dependent suppression of osteoclastogenesis, both in a coculture system of mouse bone marrow cells and osteoblasts, and in a mouse bone marrow cell culture system, and reduced bone resorption. In addition, α-LA-induced soluble RANKL was not inhibited by matrix metalloprotease inhibitors, indicating that soluble RANKL is produced by α-LA without any posttranslational processing.
Conclusion
These results suggest that α-LA suppresse |
| Key Words:
Osteoblasts, Osteoclasts, α-Lipoic acid, Proteomics, RANKL |
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