PMID- 22110749
OWN - NLM
STAT- MEDLINE
DCOM- 20120326
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 6
IP  - 11
DP  - 2011
TI  - Capric acid inhibits NO production and STAT3 activation during LPS-induced 
      osteoclastogenesis.
PG  - e27739
LID - 10.1371/journal.pone.0027739 [doi]
LID - e27739
AB  - Capric acid is a second medium-chain fatty acid, and recent studies have shown 
      that fatty acids are associated with bone density and reduce bone turnover. In 
      this study, we investigated the effects of capric acid on lipopolysaccharide 
      (LPS)-induced osteoclastogenesis in RAW264.7 cells. After treatment with capric 
      acid (1 mM), the number of tartrate resistant acid phosphatase (TRAP)-positive 
      cells decreased significantly. Capric acid reduced LPS-induced TRAP expression, 
      an osteoclast differentiation marker, without inhibiting cell viability. LPS 
      strongly upregulated inducible nitric oxide synthase (iNOS) mRNA levels and 
      nitric oxide (NO) production, whereas capric acid inhibited them. Furthermore, 
      capric acid also inhibited monocyte chemoattractant protein-1 (MCP-1) mRNA 
      expression. Subsequently, we investigated various intracellular signaling 
      proteins, including nuclear factor-kappaB (NF-kappaB), c-Jun-N-terminal kinase (JNK), 
      extracellular signal regulated kinase 1/2 (ERK1/2), and signal transducer and 
      activator of transcription 1 (STAT1) and STAT3 associated with 
      osteoclastogenesis. Capric acid had no effects on LPS-induced activation of the 
      NF-kappaB, JNK, ERK1/2, and STAT1 pathways. However, capric acid inhibited 
      LPS-induced phosphorylation of Ser(727) in STAT3. Additionally, stattic (a STAT3 
      inhibitor) inhibited LPS-induced iNOS and MCP-1 gene expression. In conclusion, 
      we demonstrated that capric acid inhibited LPS-induced osteoclastogenesis by 
      suppressing NO production via the STAT3 pathway. These results suggest that 
      capric acid has important therapeutic implications for treating bone diseases 
      associated with excessive osteoclastogenesis.
FAU - Park, Eun-Jung
AU  - Park EJ
AD  - Department of Molecular Science and Technology, Ajou University, Suwon, Korea.
FAU - Kim, Sun A
AU  - Kim SA
FAU - Choi, Yong-Min
AU  - Choi YM
FAU - Kwon, Hyuk-Kwon
AU  - Kwon HK
FAU - Shim, Wooyoung
AU  - Shim W
FAU - Lee, Gwang
AU  - Lee G
FAU - Choi, Sangdun
AU  - Choi S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111116
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Decanoic Acids)
RN  - 0 (Isoenzymes)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (STAT3 Transcription Factor)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 452VLY9402 (Serine)
RN  - 4G9EDB6V73 (decanoic acid)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 3.1.3.2 (Acid Phosphatase)
RN  - EC 3.1.3.2 (Acp5 protein, mouse)
RN  - EC 3.1.3.2 (Tartrate-Resistant Acid Phosphatase)
SB  - IM
MH  - Acid Phosphatase/metabolism
MH  - Animals
MH  - Cell Differentiation/*drug effects
MH  - Cell Line
MH  - Cell Nucleus/drug effects/metabolism
MH  - Chemokine CCL2/genetics
MH  - Decanoic Acids/*pharmacology
MH  - Isoenzymes/metabolism
MH  - JNK Mitogen-Activated Protein Kinases/metabolism
MH  - Lipopolysaccharides/*pharmacology
MH  - Mice
MH  - Mitogen-Activated Protein Kinase 1/metabolism
MH  - Mitogen-Activated Protein Kinase 3/metabolism
MH  - NF-kappa B/metabolism
MH  - Nitric Oxide/*biosynthesis
MH  - Nitric Oxide Synthase Type II/genetics
MH  - Osteoclasts/*cytology/*drug effects/enzymology/metabolism
MH  - Phosphorylation/drug effects
MH  - STAT3 Transcription Factor/chemistry/*metabolism
MH  - Serine/metabolism
MH  - Signal Transduction/drug effects
MH  - Tartrate-Resistant Acid Phosphatase
MH  - Up-Regulation/drug effects
PMC - PMC3218024
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2011/11/24 06:00
MHDA- 2012/03/27 06:00
PMCR- 2011/11/16
CRDT- 2011/11/24 06:00
PHST- 2011/05/15 00:00 [received]
PHST- 2011/10/24 00:00 [accepted]
PHST- 2011/11/24 06:00 [entrez]
PHST- 2011/11/24 06:00 [pubmed]
PHST- 2012/03/27 06:00 [medline]
PHST- 2011/11/16 00:00 [pmc-release]
AID - PONE-D-11-08556 [pii]
AID - 10.1371/journal.pone.0027739 [doi]
PST - ppublish
SO  - PLoS One. 2011;6(11):e27739. doi: 10.1371/journal.pone.0027739. Epub 2011 Nov 16.