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Licorice isoliquiritigenin suppresses RANKL-induced osteoclastogenesis in vitro and prevents inflammatory bone loss in vivo.
Int J Biochem Cell Biol. 2012 Jul; 44(7):1139-52.IJ

Abstract

Osteoclasts, bone-specialized multinucleated cells, are responsible for bone destructive diseases such as osteoporosis, periodontitis, and rheumatoid arthritis. Natural plant-derived products have received substantial attention given their potential therapeutic and preventive activities against human diseases. In the present study, we investigated the effects of isoliquiritigenin (ISL), a natural flavonoid isolated from licorice, on receptor activator of nuclear factor-κB ligand (RANKL)-induced in vitro osteoclastogenesis and inflammation-mediated bone destruction in vivo. We observed that ISL dose-dependently inhibited RANKL-induced osteoclast formation from RAW 264.7 and primary mouse bone marrow-derived macrophages (BMMs), as well as decreased the extent of lacunar resorption. Specifically, ISL targeted RANKL-induced osteoclastogenesis and F-actin rings formation at an early stage. The RANKL-stimulated mRNA expression of osteoclast-related genes and transcription factors were also diminished by ISL. Mechanistically, ISL blocked the RANKL-triggered RANK-TRAF6 association, phosphorylation of mitogen-activated protein kinases (MAPKs), inhibitor of κBα (IκBα) phosphorylation and degradation, nuclear factor-κB (NF-κB) p65 nuclear translocation, as well as activator protein (AP)-1 activation. ISL almost abrogated the nuclear factor of activated T cells (NFATc1) expression and inhibited its nuclear translocation specifically in pre-osteoclasts. Furthermore, the ectopic introduction of NFATc1 into osteoclast precursors almost reversed the ISL-elicited anti-osteoclastogenic effects. Consistent with the in vitro results, administration of ISL prevented inflammatory bone loss in mice by attenuating osteoclast activity. Taken together, our results demonstrated that ISL suppresses RANKL-induced osteoclastogenesis and inflammatory bone loss via RANK-TRAF6, MAPK, IκBα/NF-κB, and AP-1 signaling pathways. Therefore, ISL may be considered as a novel therapeutic and/or preventive strategy against lytic bone diseases.

Authors+Show Affiliations

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.No 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

22521613

Citation

Zhu, Lingxin, et al. "Licorice Isoliquiritigenin Suppresses RANKL-induced Osteoclastogenesis in Vitro and Prevents Inflammatory Bone Loss in Vivo." The International Journal of Biochemistry & Cell Biology, vol. 44, no. 7, 2012, pp. 1139-52.
Zhu L, Wei H, Wu Y, et al. Licorice isoliquiritigenin suppresses RANKL-induced osteoclastogenesis in vitro and prevents inflammatory bone loss in vivo. Int J Biochem Cell Biol. 2012;44(7):1139-52.
Zhu, L., Wei, H., Wu, Y., Yang, S., Xiao, L., Zhang, J., & Peng, B. (2012). Licorice isoliquiritigenin suppresses RANKL-induced osteoclastogenesis in vitro and prevents inflammatory bone loss in vivo. The International Journal of Biochemistry & Cell Biology, 44(7), 1139-52. https://doi.org/10.1016/j.biocel.2012.04.003
Zhu L, et al. Licorice Isoliquiritigenin Suppresses RANKL-induced Osteoclastogenesis in Vitro and Prevents Inflammatory Bone Loss in Vivo. Int J Biochem Cell Biol. 2012;44(7):1139-52. PubMed PMID: 22521613.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Licorice isoliquiritigenin suppresses RANKL-induced osteoclastogenesis in vitro and prevents inflammatory bone loss in vivo. AU - Zhu,Lingxin, AU - Wei,Hongxia, AU - Wu,Yan, AU - Yang,Shasha, AU - Xiao,Lan, AU - Zhang,Jie, AU - Peng,Bin, Y1 - 2012/04/12/ PY - 2011/12/29/received PY - 2012/03/21/revised PY - 2012/04/04/accepted PY - 2012/4/24/entrez PY - 2012/4/24/pubmed PY - 2012/12/19/medline SP - 1139 EP - 52 JF - The international journal of biochemistry & cell biology JO - Int. J. Biochem. Cell Biol. VL - 44 IS - 7 N2 - Osteoclasts, bone-specialized multinucleated cells, are responsible for bone destructive diseases such as osteoporosis, periodontitis, and rheumatoid arthritis. Natural plant-derived products have received substantial attention given their potential therapeutic and preventive activities against human diseases. In the present study, we investigated the effects of isoliquiritigenin (ISL), a natural flavonoid isolated from licorice, on receptor activator of nuclear factor-κB ligand (RANKL)-induced in vitro osteoclastogenesis and inflammation-mediated bone destruction in vivo. We observed that ISL dose-dependently inhibited RANKL-induced osteoclast formation from RAW 264.7 and primary mouse bone marrow-derived macrophages (BMMs), as well as decreased the extent of lacunar resorption. Specifically, ISL targeted RANKL-induced osteoclastogenesis and F-actin rings formation at an early stage. The RANKL-stimulated mRNA expression of osteoclast-related genes and transcription factors were also diminished by ISL. Mechanistically, ISL blocked the RANKL-triggered RANK-TRAF6 association, phosphorylation of mitogen-activated protein kinases (MAPKs), inhibitor of κBα (IκBα) phosphorylation and degradation, nuclear factor-κB (NF-κB) p65 nuclear translocation, as well as activator protein (AP)-1 activation. ISL almost abrogated the nuclear factor of activated T cells (NFATc1) expression and inhibited its nuclear translocation specifically in pre-osteoclasts. Furthermore, the ectopic introduction of NFATc1 into osteoclast precursors almost reversed the ISL-elicited anti-osteoclastogenic effects. Consistent with the in vitro results, administration of ISL prevented inflammatory bone loss in mice by attenuating osteoclast activity. Taken together, our results demonstrated that ISL suppresses RANKL-induced osteoclastogenesis and inflammatory bone loss via RANK-TRAF6, MAPK, IκBα/NF-κB, and AP-1 signaling pathways. Therefore, ISL may be considered as a novel therapeutic and/or preventive strategy against lytic bone diseases. SN - 1878-5875 UR - https://www.unboundmedicine.com/medline/citation/22521613/Licorice_isoliquiritigenin_suppresses_RANKL_induced_osteoclastogenesis_in_vitro_and_prevents_inflammatory_bone_loss_in_vivo_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1357-2725(12)00127-6 DB - PRIME DP - Unbound Medicine ER -