title: Acteoside suppresses RANKL-mediated osteoclastogenesis by inhibiting c-Fos induction and NF-κB pathway and attenuating ROS production.
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: 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.
authors: Seung-Youp
authors: SY
authors: Lee
authors: Keun-Soo
authors: KS
authors: Lee
authors: Sea Hyun
authors: SH
authors: Yi
authors: Sung-Ho
authors: SH
authors: Kook
authors: Jeong-Chae
authors: JC
authors: Lee
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001862:Bone Resorption / Q000517:prevention & control*; D002454:Cell Differentiation; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation; D005960:Glucosides / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010052:Ovariectomy; D010636:Phenols / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D053245:RANK Ligand / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000093242:Interleukin-6 Inhibitors; D059808:Polyphenols
chemical_list: D000975:Antioxidants; D005960:Glucosides; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D010636:Phenols; D016760:Proto-Oncogene Proteins c-fos; D053245:RANK Ligand; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; D000093242:Interleukin-6 Inhibitors; C494005:Nfatc1 protein, mouse; C505689:Tnfsf11 protein, mouse; C058956:acteoside; D059808:Polyphenols