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Acteoside suppresses RANKL-mediated osteoclastogenesis by inhibiting c-Fos induction and NF-κB pathway and attenuating ROS production.
PLoS One. 2013; 8(12):e80873.Plos

Abstract

Numerous studies have reported that inflammatory cytokines are important mediators for osteoclastogenesis, thereby causing excessive bone resorption and osteoporosis. Acteoside, the main active compound of Rehmannia glutinosa, which is used widely in traditional Oriental medicine, has anti-inflammatory and antioxidant potentials. In this study, we found that acteoside markedly inhibited osteoclast differentiation and formation from bone marrow macrophages (BMMs) and RAW264.7 macrophages stimulated by the receptor activator of nuclear factor-kappaB (NF-κB) ligand (RANKL). Acteoside pretreatment also prevented bone resorption by mature osteoclasts in a dose-dependent manner. Acteoside (10 µM) attenuated RANKL-stimulated activation of p38 kinase, extracellular signal-regulated kinases, and c-Jun N-terminal kinase, and also suppressed NF-κB activation by inhibiting phosphorylation of the p65 subunit and the inhibitor κBα. In addition, RANKL-mediated increases in the expression of c-Fos and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) and in the production of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 were apparently inhibited by acteoside pretreatment. Further, oral acteoside reduced ovariectomy-induced bone loss and inflammatory cytokine production to control levels. Our data suggest that acteoside inhibits osteoclast differentiation and maturation from osteoclastic precursors by suppressing RANKL-induced activation of mitogen-activated protein kinases and transcription factors such as NF-κB, c-Fos, and NFATc1. Collectively, these results suggest that acteoside may act as an anti-resorptive agent to reduce bone loss by blocking osteoclast activation.

Authors+Show Affiliations

Research Institute of Clinical Medicine of Chonbuk National University, Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Chonbuk, South Korea ; Department of Orthodontics, Institute of Oral Biosciences and School of Dentistry, Chonbuk National University, Jeonju, Chonbuk, South Korea.No 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

24324641

Citation

Lee, Seung-Youp, et al. "Acteoside Suppresses RANKL-mediated Osteoclastogenesis By Inhibiting c-Fos Induction and NF-κB Pathway and Attenuating ROS Production." PloS One, vol. 8, no. 12, 2013, pp. e80873.
Lee SY, Lee KS, Yi SH, et al. Acteoside suppresses RANKL-mediated osteoclastogenesis by inhibiting c-Fos induction and NF-κB pathway and attenuating ROS production. PLoS ONE. 2013;8(12):e80873.
Lee, S. Y., Lee, K. S., Yi, S. H., Kook, S. H., & Lee, J. C. (2013). Acteoside suppresses RANKL-mediated osteoclastogenesis by inhibiting c-Fos induction and NF-κB pathway and attenuating ROS production. PloS One, 8(12), e80873. https://doi.org/10.1371/journal.pone.0080873
Lee SY, et al. Acteoside Suppresses RANKL-mediated Osteoclastogenesis By Inhibiting c-Fos Induction and NF-κB Pathway and Attenuating ROS Production. PLoS ONE. 2013;8(12):e80873. PubMed PMID: 24324641.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Acteoside suppresses RANKL-mediated osteoclastogenesis by inhibiting c-Fos induction and NF-κB pathway and attenuating ROS production. AU - Lee,Seung-Youp, AU - Lee,Keun-Soo, AU - Yi,Sea Hyun, AU - Kook,Sung-Ho, AU - Lee,Jeong-Chae, Y1 - 2013/12/04/ PY - 2013/08/08/received PY - 2013/10/07/accepted PY - 2013/12/11/entrez PY - 2013/12/11/pubmed PY - 2014/9/10/medline SP - e80873 EP - e80873 JF - PloS one JO - PLoS ONE VL - 8 IS - 12 N2 - Numerous studies have reported that inflammatory cytokines are important mediators for osteoclastogenesis, thereby causing excessive bone resorption and osteoporosis. Acteoside, the main active compound of Rehmannia glutinosa, which is used widely in traditional Oriental medicine, has anti-inflammatory and antioxidant potentials. In this study, we found that acteoside markedly inhibited osteoclast differentiation and formation from bone marrow macrophages (BMMs) and RAW264.7 macrophages stimulated by the receptor activator of nuclear factor-kappaB (NF-κB) ligand (RANKL). Acteoside pretreatment also prevented bone resorption by mature osteoclasts in a dose-dependent manner. Acteoside (10 µM) attenuated RANKL-stimulated activation of p38 kinase, extracellular signal-regulated kinases, and c-Jun N-terminal kinase, and also suppressed NF-κB activation by inhibiting phosphorylation of the p65 subunit and the inhibitor κBα. In addition, RANKL-mediated increases in the expression of c-Fos and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) and in the production of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 were apparently inhibited by acteoside pretreatment. Further, oral acteoside reduced ovariectomy-induced bone loss and inflammatory cytokine production to control levels. Our data suggest that acteoside inhibits osteoclast differentiation and maturation from osteoclastic precursors by suppressing RANKL-induced activation of mitogen-activated protein kinases and transcription factors such as NF-κB, c-Fos, and NFATc1. Collectively, these results suggest that acteoside may act as an anti-resorptive agent to reduce bone loss by blocking osteoclast activation. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/24324641/Acteoside_suppresses_RANKL_mediated_osteoclastogenesis_by_inhibiting_c_Fos_induction_and_NF_κB_pathway_and_attenuating_ROS_production_ L2 - http://dx.plos.org/10.1371/journal.pone.0080873 DB - PRIME DP - Unbound Medicine ER -