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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.
Mol Cells. 2014 Aug; 37(8):598-604.MC

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+Show Affiliations

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.Clinical Trial Center, Kyungpook National University Hospital, Daegu 700-721, Korea.Department of Orthopedic Surgery, School of Medicine, Kyungpook National University, Daegu 700-422, Korea.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.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25134536

Citation

Kim, Hyun-Ju, et al. "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." Molecules and Cells, vol. 37, no. 8, 2014, pp. 598-604.
Kim HJ, Yoon HJ, Kim SY, et al. 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. Mol Cells. 2014;37(8):598-604.
Kim, H. J., Yoon, H. J., Kim, S. Y., & Yoon, Y. R. (2014). 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. Molecules and Cells, 37(8), 598-604. https://doi.org/10.14348/molcells.2014.0153
Kim HJ, et al. 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. Mol Cells. 2014;37(8):598-604. PubMed PMID: 25134536.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Kim,Hyun-Ju, AU - Yoon,Hye-Jin, AU - Kim,Shin-Yoon, AU - Yoon,Young-Ran, Y1 - 2014/08/18/ PY - 2014/06/05/received PY - 2014/07/02/revised PY - 2014/07/07/accepted PY - 2014/8/20/entrez PY - 2014/8/20/pubmed PY - 2015/6/3/medline KW - NF-κB KW - NFATc1 KW - apoptosis KW - capric acid KW - cytoskeletal organization KW - osteoclast SP - 598 EP - 604 JF - Molecules and cells JO - Mol Cells VL - 37 IS - 8 N2 - 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. SN - 0219-1032 UR - https://www.unboundmedicine.com/medline/citation/25134536/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_ L2 - https://dx.doi.org/10.14348/molcells.2014.0153 DB - PRIME DP - Unbound Medicine ER -