title: The Inhibitory Effect of Angelica tenuissima Water Extract on Receptor Activator of Nuclear Factor-Kappa-B Ligand-Induced Osteoclast Differentiation and Bone Resorbing Activity of Mature Osteoclasts.
abstract: Angelica tenuissima has been traditionally used in oriental medicine for its therapeutic effects in headache, toothache, and flu symptoms. It also exerts anti-inflammatory activity via the inhibition of the expression of cyclooxygenase-2 (COX-2). However, the effect of Angelica tenuissima on osteoclast differentiation has not been identified until recently. In this study, we first confirmed that Angelica tenuissima water extract (ATWE) significantly interrupted the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells (MNCs) in a dose-dependent manner without any cytotoxicity. Next, we clarified the underlying mechanisms linking the suppression effects of ATWE on the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis. At the molecular level, ATWE induced the dephosphorylation of c-Jun N-terminal kinase (JNK) and Akt and decreased the degradation of IκB in RANKL-dependent early signaling pathways. Subsequently, ATWE caused impaired activation of the protein and mRNA levels of c-Fos and nuclear factor of activated T cell c1 (NFATc1). Moreover, the disassembly of filamentous actin (F-actin) ring and anti-resorptive activity of mature osteoclasts were triggered by ATWE treatment. Although ATWE did not enhance osteogenesis in primary osteoblasts, our results showed that ATWE is a potential candidate for anti-resorptive agent in osteoporosis, a common metabolic bone disorder.
authors.affiliation: Department of Anatomy, Wonkwang University, Iksan, Jeonbuk, Republic of Korea.|BK21plus Program and Department of Smart Life-Care Convergence, Graduate School, Wonkwang University, Iksan, Jeonbuk, Republic of Korea.
authors.forename: Sung-Jun
authors.initials: SJ
authors.lastname: Ahn
authors.affiliation: Department of Anatomy, Wonkwang University, Iksan, Jeonbuk, Republic of Korea.|BK21plus Program and Department of Smart Life-Care Convergence, Graduate School, Wonkwang University, Iksan, Jeonbuk, Republic of Korea.
authors.forename: Jong Min
authors.initials: JM
authors.lastname: Baek
authors.affiliation: Department of Anatomy, Wonkwang University, Iksan, Jeonbuk, Republic of Korea.|BK21plus Program and Department of Smart Life-Care Convergence, Graduate School, Wonkwang University, Iksan, Jeonbuk, Republic of Korea.
authors.forename: Yoon-Hee
authors.initials: YH
authors.lastname: Cheon
authors.affiliation: Department of Anatomy, Wonkwang University, Iksan, Jeonbuk, Republic of Korea.|BK21plus Program and Department of Smart Life-Care Convergence, Graduate School, Wonkwang University, Iksan, Jeonbuk, Republic of Korea.
authors.forename: Sun-Hyang
authors.initials: SH
authors.lastname: Park
authors.affiliation: Imaging Science-Based Lung and Bone Diseases Research Center, Wonkwang University, Iksan, Jeonbuk, Republic of Korea.|Department of Rheumatology, Wonkwang University, Iksan, Jeonbuk, Republic of Korea.|Institute for Skeletal Disease, Wonkwang University, Iksan, Jeonbuk, Republic of Korea.
authors.forename: Myeung Su
authors.initials: MS
authors.lastname: Lee
authors.affiliation: Department of Anatomy, Wonkwang University, Iksan, Jeonbuk, Republic of Korea.|BK21plus Program and Department of Smart Life-Care Convergence, Graduate School, Wonkwang University, Iksan, Jeonbuk, Republic of Korea.|Imaging Science-Based Lung and Bone Diseases Research Center, Wonkwang University, Iksan, Jeonbuk, Republic of Korea.|Institute for Skeletal Disease, Wonkwang University, Iksan, Jeonbuk, Republic of Korea.
authors.forename: Jaemin
authors.initials: J
authors.lastname: Oh
authors.affiliation: Imaging Science-Based Lung and Bone Diseases Research Center, Wonkwang University, Iksan, Jeonbuk, Republic of Korea.
authors.forename: Ju-Young
authors.initials: JY
authors.lastname: Kim
mesh_terms: D000135:Acid Phosphatase; D029969:Angelica / Q000737:chemistry*; D000818:Animals; D001862:Bone Resorption / Q000188:drug therapy*; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D015726:Giant Cells / Q000187:drug effects; D051550:I-kappa B Kinase / Q000378:metabolism; D007527:Isoenzymes; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D051379:Mice; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects*; D010766:Phosphorylation; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000494:pharmacology*; D000071681:Tartrate-Resistant Acid Phosphatase; D014867:Water
chemical_list: D007527:Isoenzymes; D010936:Plant Extracts; D053246:Receptor Activator of Nuclear Factor-kappa B; D014867:Water; D051550:I-kappa B Kinase; D048031:JNK Mitogen-Activated Protein Kinases; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase
keywords: Angelica tenuissima; Bone Resorption; Osteoclast; Osteoporosis; RANKL