title: Echinocystic acid inhibits RANKL-induced osteoclastogenesis by regulating NF-κB and ERK signaling pathways.
abstract: Receptor activator of nuclear factor-κB ligand (RANKL) is a key factor in the differentiation and activation of osteoclasts. Echinocystic acid (EA), a pentacyclic triterpene isolated from the fruits of Gleditsia sinensis Lam, was reported to prevent reduction of bone mass and strength and improve the cancellous bone structure and biochemical properties in ovariectomy rats. However, the molecular mechanism of EA on the osteoclast formation has not been reported. The purpose of this study was to investigate the effects and mechanism of EA on RANKL-induced osteoclastogenesis. Our results showed that EA inhibited the formation of osteoclast, as well as the expression of osteoclastogenesis-related marker proteins in bone marrow macrophages (BMMs). At molecular levels, EA inhibited RANKL-induced NF-κB activation and ERK phosphorylation in BMMs. In conclusion, the present study demonstrated that EA can suppress osteoclastogenesis in vitro. Moreover, we clarified that these inhibitory effects of EA occur through suppression of NF-κB and ERK activation. Therefore, EA may be a potential agent in the treatment of osteoclast-related diseases such as osteoporosis.
authors.affiliation: Rehabilitation Center, First Affiliated Hospital of Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi Province, China. Electronic address: jianhui_yangxa@163.com.
authors.forename: Jian-Hui
authors.initials: JH
authors.lastname: Yang
authors.affiliation: Department of Dermatology, the 451st Hospital of People's Liberation Army, Xi'an 710054, Shaanxi Province, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.affiliation: Rehabilitation Center, First Affiliated Hospital of Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi Province, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Rehabilitation Center, First Affiliated Hospital of Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi Province, China.
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Lv
authors.affiliation: Rehabilitation Center, First Affiliated Hospital of Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi Province, China.
authors.forename: Hui-Yong
authors.initials: HY
authors.lastname: Nie
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D009828:Oleanolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*
chemical_list: D016328:NF-kappa B; D009828:Oleanolic Acid; C022999:echinocystic acid
keywords: Bone marrow macrophages (BMMs); Echinocystic acid (EA); Receptor activator of nuclear factor κB ligand (RANKL)