title: Mollugin from Rubea cordifolia suppresses receptor activator of nuclear factor-κB ligand-induced osteoclastogenesis and bone resorbing activity in vitro and prevents lipopolysaccharide-induced bone loss in vivo.
abstract: Osteopenic diseases, such as osteoporosis, are characterized by progressive and excessive bone resorption mediated by enhanced receptor activator of nuclear factor-κB ligand (RANKL) signaling. Therefore, downregulation of RANKL downstream signals may be a valuable approach for the treatment of bone loss-associated disorders. In this study, we investigated the effects of the naphthohydroquinone mollugin on osteoclastogenesis and its function in vitro and in vivo. Mollugin efficiently suppressed RANKL-induced osteoclast differentiation of bone marrow macrophages (BMMs) and bone resorbing activity of mature osteoclasts by inhibiting RANKL-induced c-Fos and NFATc1 expression. Mollugin reduced the phosphorylation of signaling pathways activated in the early stages of osteoclast differentiation, including the MAP kinase, Akt, and GSK3β and inhibited the expression of different genes associated with osteoclastogenesis, such as OSCAR, TRAP, DC-STAMP, OC-STAMP, integrin αν, integrin β3, cathepsin K, and ICAM-1. Furthermore, mice treated with mollugin showed significant restoration of lipopolysaccharide (LPS)-induced bone loss as indicated by micro-CT and histological analysis of femurs. Consequently, these results suggested that mollugin could be a novel therapeutic candidate for bone loss-associated disorders including osteoporosis, rheumatoid arthritis, and periodontitis.
authors: Department of Anatomy, School of Medicine, Wonkwang University, Iksan, Republic of Korea; BK21plus Program and Department of Smart Life-care Convergence, Graduate School, Wonkwang University, Iksan, Republic of Korea.
authors: Jong Min
authors: JM
authors: Baek
authors: Imaging Science-based Lung and Bone Diseases Research Center, Wonkwang University, Iksan, Republic of Korea.
authors: Ju-Young
authors: JY
authors: Kim
authors: College of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Republic of Korea.
authors: Youngeun
authors: Y
authors: Jung
authors: Laboratory of Translational Therapeutics, Pharmacology Research Center, Division of Drug Discovery Research, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea; Department of Biology, Chungnam National University, Daejeon, Republic of Korea.
authors: Seong-Hee
authors: SH
authors: Moon
authors: Department of Anatomy, School of Medicine, Wonkwang University, Iksan, Republic of Korea.
authors: Min Kyu
authors: MK
authors: Choi
authors: Laboratory of Translational Therapeutics, Pharmacology Research Center, Division of Drug Discovery Research, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea.
authors: Seong Hwan
authors: SH
authors: Kim
authors: Department of Anatomy, School of Medicine, Wonkwang University, Iksan, Republic of Korea; Imaging Science-based Lung and Bone Diseases Research Center, Wonkwang University, Iksan, Republic of Korea; Department of Rheumatology, Wonkwang University, Iksan, Republic of Korea.
authors: Myeung Su
authors: MS
authors: Lee
authors: College of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Republic of Korea. Electronic address: ikyonkim@yonsei.ac.kr.
authors: Ikyon
authors: I
authors: Kim
authors: Department of Anatomy, School of Medicine, Wonkwang University, Iksan, Republic of Korea; BK21plus Program and Department of Smart Life-care Convergence, Graduate School, Wonkwang University, Iksan, Republic of Korea; Imaging Science-based Lung and Bone Diseases Research Center, Wonkwang University, Iksan, Republic of Korea. Electronic address: jmoh@wku.ac.kr.
authors: Jaemin
authors: J
authors: Oh
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000188:drug therapy*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects; D008813:Mice, Inbred ICR; D010010:Osteoclasts / Q000187:drug effects*; D011714:Pyrans / Q000494:pharmacology*; D053245:RANK Ligand / Q000378:metabolism*; D045470:Rubia / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D008070:Lipopolysaccharides; D011714:Pyrans; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; C046245:rubimaillin
keywords: Bone resorption; Mollugin; NFATc1; Osteoclastogenesis; Rubea cordifolia