title: α-Tocopheryl Succinate Inhibits Osteoclast Formation by Suppressing Receptor Activator of Nuclear Factor-kappaB Ligand (RANKL) Expression and Bone Resorption.
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 (αTP-suc) have demonstrated potent anti-cancer activities in vitro and in vivo. However, the effects of αTP-suc on osteoclast formation and bone resorption remain unknown. Thus, in this study, we examined the effects of αTP-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 αTP-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
  αTP-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 αTP-suc prevented IL-1-mediated osteoclast formation and bone loss in vivo.
  
  
  CONCLUSIONS
  Our findings suggest that αTP-suc may have therapeutic value for treating and preventing bone-resorptive diseases, such as osteoporosis.
authors: Department of Cell and Developmental Biology, DRI, School of Dentistry, Seoul National University, Seoul, Korea.
authors: Ha-Neui
authors: HN
authors: Kim
authors: Department of Cell and Developmental Biology, DRI, School of Dentistry, Seoul National University, Seoul, Korea.
authors: Jong-Ho
authors: JH
authors: Lee
authors: Department of Cell and Developmental Biology, DRI, School of Dentistry, Seoul National University, Seoul, Korea.
authors: Won Jong
authors: WJ
authors: Jin
authors: Department of Cell and Developmental Biology, DRI, School of Dentistry, Seoul National University, Seoul, Korea.
authors: Zang Hee
authors: ZH
authors: Lee
keywords: Alpha-tocopheryl succinate; Interleukin-1; Osteoclast; Osteoporosis; RANKL