alpha-Tocopheryl Succinate Inhibits Osteoclast Formation by Suppressing Receptor Activator of Nuclear Factor-kappaB Ligand (RANKL) Expression and Bone Resorption.
10.11005/jbm.2012.19.2.111
- Author:
Ha Neui KIM
1
;
Jong Ho LEE
;
Won Jong JIN
;
Zang Hee LEE
Author Information
1. Department of Cell and Developmental Biology, DRI, School of Dentistry, Seoul National University, Seoul, Korea. zang1959@snu.ac.kr
- Publication Type:In Vitro ; Original Article
- Keywords:
Alpha-tocopheryl succinate;
Interleukin-1;
Osteoclast;
Osteoporosis;
RANKL
- MeSH:
Acid Phosphatase;
Animals;
Bone Marrow Cells;
Bone Resorption;
Coculture Techniques;
Collagen;
Culture Media;
Cytokines;
Dimethyl Sulfoxide;
Injections, Intraperitoneal;
Interleukin-1;
Isoenzymes;
Mice;
Mice, Inbred ICR;
Osteoblasts;
Osteoclasts;
Osteoporosis;
Porifera;
RANK Ligand;
Receptor Activator of Nuclear Factor-kappa B;
RNA, Messenger;
Safrole;
Skull;
Succinic Acid
- From:Journal of Bone Metabolism
2012;19(2):111-120
- CountryRepublic of Korea
- Language:English
-
Abstract:
OBJECTIVE: Osteoclasts are bone-resorbing multinucleated cells derived from the monocyte/macrophage lineage during normal and pathological bone turnover. Recently, several studies revealed that alpha-tocopheryl succinate (alphaTP-suc) have demonstrated potent anti-cancer activities in vitro and in vivo. However, the effects of alphaTP-suc on osteoclast formation and bone resorption remain unknown. Thus, in this study, we examined the effects of alphaTP-suc on osteoclast differentiation and bone resorbing activity in inflammatory bone loss model. METHODS: Osteoclast differentiation assay was performed by cocultures of mouse bone marrow cells and calvarial osteoblasts in culture media including interleukin-1 (IL-1). Osteoclasts were stained for tartrate-resistant acid phosphatase (TRAP). The level of receptor activator of nuclear factor-kappaB ligand (RANKL) mRNA was determined by reverse transcriptase-polymerase chain reaction (RT-PCR). ICR mice were administered an intraperitoneal injections of alphaTP-suc or dimethyl sulfoxide (DMSO) 1 day before the implantation of a freeze-dried collagen sponge loaded with phosphate-buffered saline (PBS) or IL-1 over the calvariae and every other day for 7 days. The whole calvariae were obtained and analyzed by micro-computed tomography (CT) scanning, and stained for TRAP. RESULTS: alphaTP-suc inhibits osteoclast formation in cocultures stimulated by IL-1 and decreased the level of expression of RANKL mRNA in osteoblasts. In addition, administered intraperitoneal injections of alphaTP-suc prevented IL-1-mediated osteoclast formation and bone loss in vivo. CONCLUSION: Our findings suggest that alphaTP-suc may have therapeutic value for treating and preventing bone-resorptive diseases, such as osteoporosis.
