Tags

Type your tag names separated by a space and hit enter

Formononetin attenuates osteoclastogenesis via suppressing the RANKL-induced activation of NF-κB, c-Fos, and nuclear factor of activated T-cells cytoplasmic 1 signaling pathway.
J Nat Prod. 2014 Nov 26; 77(11):2423-31.JN

Abstract

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)-α, interleukin (IL)-1β, IL-6, monocyte chemoattractant protein-1 (MCP-1), regulated on activation normal T cell expressed and secreted (RANTES), and macrophage inflammatory protein-1α (MIP-1α) in a concentration-dependent manner. These effects were accompanied by a decrease in RANKL-induced activation of the NF-κB p65 subunit, degradation of inhibitor κBα (IκBα), induction of NF-κB, and phosphorylation of AKT, extracellular-signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK). NF-κB 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.

Authors+Show Affiliations

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.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

25397676

Citation

Huh, Jeong-Eun, et al. "Formononetin Attenuates Osteoclastogenesis Via Suppressing the RANKL-induced Activation of NF-κB, c-Fos, and Nuclear Factor of Activated T-cells Cytoplasmic 1 Signaling Pathway." Journal of Natural Products, vol. 77, no. 11, 2014, pp. 2423-31.
Huh JE, Lee WI, Kang JW, et al. Formononetin attenuates osteoclastogenesis via suppressing the RANKL-induced activation of NF-κB, c-Fos, and nuclear factor of activated T-cells cytoplasmic 1 signaling pathway. J Nat Prod. 2014;77(11):2423-31.
Huh, J. E., Lee, W. I., Kang, J. W., Nam, D., Choi, D. Y., Park, D. S., Lee, S. H., & Lee, J. D. (2014). Formononetin attenuates osteoclastogenesis via suppressing the RANKL-induced activation of NF-κB, c-Fos, and nuclear factor of activated T-cells cytoplasmic 1 signaling pathway. Journal of Natural Products, 77(11), 2423-31. https://doi.org/10.1021/np500417d
Huh JE, et al. Formononetin Attenuates Osteoclastogenesis Via Suppressing the RANKL-induced Activation of NF-κB, c-Fos, and Nuclear Factor of Activated T-cells Cytoplasmic 1 Signaling Pathway. J Nat Prod. 2014 Nov 26;77(11):2423-31. PubMed PMID: 25397676.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Formononetin attenuates osteoclastogenesis via suppressing the RANKL-induced activation of NF-κB, c-Fos, and nuclear factor of activated T-cells cytoplasmic 1 signaling pathway. AU - Huh,Jeong-Eun, AU - Lee,Wong In, AU - Kang,Jung Won, AU - Nam,Dongwoo, AU - Choi,Do-Young, AU - Park,Dong-Suk, AU - Lee,Sang Hoon, AU - Lee,Jae-Dong, Y1 - 2014/11/14/ PY - 2014/11/15/entrez PY - 2014/11/15/pubmed PY - 2015/7/15/medline SP - 2423 EP - 31 JF - Journal of natural products JO - J Nat Prod VL - 77 IS - 11 N2 - 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)-α, interleukin (IL)-1β, IL-6, monocyte chemoattractant protein-1 (MCP-1), regulated on activation normal T cell expressed and secreted (RANTES), and macrophage inflammatory protein-1α (MIP-1α) in a concentration-dependent manner. These effects were accompanied by a decrease in RANKL-induced activation of the NF-κB p65 subunit, degradation of inhibitor κBα (IκBα), induction of NF-κB, and phosphorylation of AKT, extracellular-signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK). NF-κB 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. SN - 1520-6025 UR - https://www.unboundmedicine.com/medline/citation/25397676/Formononetin_attenuates_osteoclastogenesis_via_suppressing_the_RANKL_induced_activation_of_NF_κB_c_Fos_and_nuclear_factor_of_activated_T_cells_cytoplasmic_1_signaling_pathway_ L2 - https://doi.org/10.1021/np500417d DB - PRIME DP - Unbound Medicine ER -