title: 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.
abstract: 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-κB ligand (RANKL) and macrophage colony-stimulating factor (MCSF). Capric acid inhibited RANKL-mediated osteoclastogenesis in bone marrow-derived macrophages and suppressed RANKL-induced IκBα phosphorylation, p65 nuclear translocation, and NF-κB 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.
authors.affiliation: Department of Molecular Medicine, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 700-422, Korea ; Clinical Trial Center, Kyungpook National University Hospital, Daegu 700-721, Korea.
authors.forename: Hyun-Ju
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Clinical Trial Center, Kyungpook National University Hospital, Daegu 700-721, Korea.
authors.forename: Hye-Jin
authors.initials: HJ
authors.lastname: Yoon
authors.affiliation: Department of Orthopedic Surgery, School of Medicine, Kyungpook National University, Daegu 700-422, Korea.
authors.forename: Shin-Yoon
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Molecular Medicine, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 700-422, Korea ; Clinical Trial Center, Kyungpook National University Hospital, Daegu 700-721, Korea.
authors.forename: Young-Ran
authors.initials: YR
authors.lastname: Yoon
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000648:ultrastructure; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D001862:Bone Resorption / Q000517:prevention & control; D002454:Cell Differentiation; D002470:Cell Survival / Q000187:drug effects; D003652:Decanoic Acids / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D005269:Femur / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D000072000:NF-KappaB Inhibitor alpha; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D053245:RANK Ligand / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D013977:Tibia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D050071:Bone Density Conservation Agents; D003652:Decanoic Acids; D020672:I-kappa B Proteins; D008565:Membrane Proteins; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; C000606205:Nfkbia protein, mouse; D011518:Proto-Oncogene Proteins; D053245:RANK Ligand; C498144:Rela protein, mouse; C505689:Tnfsf11 protein, mouse; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha; C031071:decanoic acid; D016173:Macrophage Colony-Stimulating Factor; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: NF-κB; NFATc1; apoptosis; capric acid; cytoskeletal organization; osteoclast