PMID- 25397676
OWN - NLM
STAT- MEDLINE
DCOM- 20150708
LR  - 20220321
IS  - 1520-6025 (Electronic)
IS  - 0163-3864 (Linking)
VI  - 77
IP  - 11
DP  - 2014 Nov 26
TI  - Formononetin attenuates osteoclastogenesis via suppressing the RANKL-induced 
      activation of NF-kappaB, c-Fos, and nuclear factor of activated T-cells cytoplasmic 1 
      signaling pathway.
PG  - 2423-31
LID - 10.1021/np500417d [doi]
AB  - Formononetin (1), a plant-derived phytoestrogen, possesses bone protective 
      properties. To address the potential therapeutic efficacy and mechanism of action 
      of 1, we investigated its antiosteoclastogenic activity and its effect on nuclear 
      factor-kappaB ligand (RANKL)-induced bone-marrow-derived macrophages (BMMs). 
      Compound 1 markedly inhibited RANKL-induced osteoclast differentiation in the 
      absence of cytotoxicity, by regulating the expression of osteoprotegerin (OPG) 
      and RANKL in BMMs and in cocultured osteoblasts. Compound 1 significantly 
      inhibited RANKL-induced tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, 
      monocyte chemoattractant protein-1 (MCP-1), regulated on activation normal T cell 
      expressed and secreted (RANTES), and macrophage inflammatory protein-1alpha (MIP-1alpha) 
      in a concentration-dependent manner. These effects were accompanied by a decrease 
      in RANKL-induced activation of the NF-kappaB p65 subunit, degradation of inhibitor 
      kappaBalpha (IkappaBalpha), induction of NF-kappaB, and phosphorylation of AKT, extracellular-signal 
      regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated 
      protein kinase (p38 MAPK). NF-kappaB siRNA suppressed AKT, ERK, JNK, and p38 MAPK 
      phosphorylation. Furthermore, 1 significantly suppressed c-Fos and nuclear factor 
      of activated T-cells cytoplasmic 1 (NFATc1), key transcription factors during 
      osteoclastogenesis. SP600125, a specific inhibitor of JNK, reduced RANKL-induced 
      expression of phospho-c-Jun, c-Fos, and NFATc1 and inhibited osteoclast 
      formation. These results suggested that 1 acted as an antiresorption agent by 
      blocking osteoclast activation.
FAU - Huh, Jeong-Eun
AU  - Huh JE
AD  - Oriental Medicine Research Center for Bone and Joint Disease, East-West Bone & 
      Joint Research Institute, Kyung Hee University , 149, Sangil-dong, Gangdong-gu, 
      Seoul, Korea.
FAU - Lee, Wong In
AU  - Lee WI
FAU - Kang, Jung Won
AU  - Kang JW
FAU - Nam, Dongwoo
AU  - Nam D
FAU - Choi, Do-Young
AU  - Choi DY
FAU - Park, Dong-Suk
AU  - Park DS
FAU - Lee, Sang Hoon
AU  - Lee SH
FAU - Lee, Jae-Dong
AU  - Lee JD
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141114
PL  - United States
TA  - J Nat Prod
JT  - Journal of natural products
JID - 7906882
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-6)
RN  - 0 (Isoflavones)
RN  - 0 (NF-kappa B)
RN  - 0 (Phytoestrogens)
RN  - 0 (Proto-Oncogene Proteins c-fos)
RN  - 0 (RANK Ligand)
RN  - 295DQC67BJ (formononetin)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Chemokine CCL2
MH  - Interleukin-6/metabolism
MH  - Isoflavones/chemistry/*pharmacology
MH  - JNK Mitogen-Activated Protein Kinases/metabolism
MH  - Macrophages/drug effects
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Molecular Structure
MH  - NF-kappa B/*antagonists & inhibitors
MH  - Osteoblasts/drug effects
MH  - Osteoclasts/drug effects
MH  - Phytoestrogens/chemistry/*pharmacology
MH  - Proto-Oncogene Proteins c-fos/drug effects
MH  - RANK Ligand/pharmacology
MH  - Signal Transduction/drug effects
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
EDAT- 2014/11/15 06:00
MHDA- 2015/07/15 06:00
CRDT- 2014/11/15 06:00
PHST- 2014/11/15 06:00 [entrez]
PHST- 2014/11/15 06:00 [pubmed]
PHST- 2015/07/15 06:00 [medline]
AID - 10.1021/np500417d [doi]
PST - ppublish
SO  - J Nat Prod. 2014 Nov 26;77(11):2423-31. doi: 10.1021/np500417d. Epub 2014 Nov 14.