title: Saikosaponin a inhibits RANKL-induced osteoclastogenesis by suppressing NF-κB and MAPK pathways.
abstract: Inflammatory cytokines play an important role in osteoclastogenesis. Saikosaponin a (SSa) possesses anti-inflammatory activity. However, the role of SSa in osteoporosis is still unclear. Therefore, the objective of this study was to investigate the effects of SSa on receptor activator of the nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis and signaling pathway by in vitro assay. In mouse bone marrow monocytes (BMMs), SSa suppressed RANKL plus macrophage colony-stimulating factor (M-CSF)-induced osteoclast differentiation in a dose-dependent manner. Moreover, SSa decreased osteoclastogenesis-related marker proteins expression, including NFATc1, c-fos and cathepsin K. At molecular levels, SSa inhibited RANKL-induced IκBα phosphorylation, p65 phosphorylation and NF-κB luciferase activity in RAW264.7 cells. And SSa also suppressed RANKL-induced p-38, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) phosphorylation. Taken together, these findings suggest that SSa suppresses osteoclastogenesis through inhibiting RANKL-induced p-38, ERK, JNK and NF-κB activation. SSa is a novel agent in the treatment of osteoclast-related diseases, such as osteoporosis.
authors.affiliation: The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
authors.forename: Chi
authors.initials: C
authors.lastname: Zhou
authors.affiliation: The 2nd Traditional Chinese Medicine Hospital of Guangdong Province, Guangdong Province, China.
authors.forename: Wengang
authors.initials: W
authors.lastname: Liu
authors.affiliation: The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.affiliation: The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China. Electronic address: haibin_wanggz@163.com.
authors.forename: Haibin
authors.initials: H
authors.lastname: Wang
authors.affiliation: The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
authors.forename: Qunqun
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Institute of TCM Diagnostic, Hunan University of Chinese Medicine, Changsha, Hunan 410007, China. Electronic address: houpan_song@163.com.
authors.forename: Houpan
authors.initials: H
authors.lastname: Song
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000502:physiology; D029972:Bupleurum / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008516:Medicine, Chinese Traditional; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D010010:Osteoclasts / Q000187:drug effects* / Q000502:physiology; D010024:Osteoporosis / Q000188:drug therapy* / Q000276:immunology; D053245:RANK Ligand / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D007166:Immunosuppressive Agents; D016328:NF-kappa B; D053245:RANK Ligand; D012503:Saponins; D009828:Oleanolic Acid; D048051:p38 Mitogen-Activated Protein Kinases; C025759:saikosaponin D
keywords: MAPK; NF-κB; Osteoclast; RANKL; Saikosaponin a