DOI QR코드

DOI QR Code

A Medium-Chain Fatty Acid, Capric Acid, Inhibits RANKL-Induced Osteoclast Differentiation via the Suppression of NF-κB Signaling and Blocks Cytoskeletal Organization and Survival in Mature Osteoclasts

  • Kim, Hyun-Ju (Department of Molecular Medicine, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University) ;
  • Yoon, Hye-Jin (Clinical Trial Center, Kyungpook National University Hospital) ;
  • Kim, Shin-Yoon (Department of Orthopedic Surgery, School of Medicine, Kyungpook National University) ;
  • Yoon, Young-Ran (Department of Molecular Medicine, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University)
  • 투고 : 2014.06.05
  • 심사 : 2014.07.07
  • 발행 : 2014.08.31

초록

Fatty acids, important components of a normal diet, have been reported to play a role in bone metabolism. Osteoclasts are bone-resorbing cells that are responsible for many bone-destructive diseases such as osteoporosis. In this study, we investigated the impact of a medium-chain fatty acid, capric acid, on the osteoclast differentiation, function, and survival induced by receptor activator of NF-${\kappa}B$ ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). Capric acid inhibited RANKL-mediated osteoclastogenesis in bone marrow-derived macrophages and suppressed RANKL-induced $I{\kappa}B{\alpha}$ phosphorylation, p65 nuclear translocation, and NF-${\kappa}B$ transcriptional activity. Capric acid further blocked the RANKL-stimulated activation of ERK without affecting JNK or p38. The induction of NFATc1 in response to RANKL was also attenuated by capric acid. In addition, capric acid abrogated M-CSF and RANKL-mediated cytoskeleton reorganization, which is crucial for the efficient bone resorption of osteoclasts. Capric acid also increased apoptosis in mature osteoclasts through the induction of Bim expression and the suppression of ERK activation by M-CSF. Together, our results reveal that capric acid has inhibitory effects on osteoclast development. We therefore suggest that capric acid may have potential therapeutic implications for the treatment of bone resorption-associated disorders.

키워드

참고문헌

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