title: Curcumol suppresses RANKL-induced osteoclast formation by attenuating the JNK signaling pathway.
abstract: Osteoclasts, derived from hemopoietic progenitors of the monocyte/macrophage lineage, have a unique role in bone resorption, and are considered a potential therapeutic target in the treatment of such pathologic bone diseases as osteoporosis, rheumatoid arthritis, and periodontitis. In the present study, we demonstrate that curcumol, one of the major components of the essential oil of Rhizoma Curcumae, exhibits an inhibitory effect on receptor activator of nuclear factor kappaB ligand (RANKL)-induced osteoclast differentiation with both bone marrow-derived macrophages and RAW264.7 cells in a dose-dependent manner. In addition, RANKL-induced mRNA expression of osteoclast-specific genes, such as tartrate-resistant acid phosphatase, calcitonin receptor, and cathepsin K, is prominently reduced in the presence of curcumol. Furthermore, the molecular mechanism of action was investigated, and curcumol inhibited osteoclastogenesis by specifically impairing RANKL-induced c-Jun N-terminal kinase (JNK)/activator protein-1 (AP-1) signaling, which was further identified in rescue studies by means of anisomycin, a JNK signaling-specific activator. Taken together, these findings suggest that curcumol suppresses RANKL-induced osteoclast differentiation through the JNK/AP-1 signaling pathway, and may be useful as a therapeutic treatment for bone resorption-associated diseases.
authors.affiliation: Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address: yu.mingxiang@zs-hospital.sh.cn.
authors.forename: Mingxiang
authors.initials: M
authors.lastname: Yu
authors.affiliation: Department of Endocrinology and Metabolism, Hainan Provincial Nong Ken Hospital, Hainan, China.
authors.forename: Xianying
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Chaoyang
authors.initials: C
authors.lastname: Lv
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Songjiang District Central Hospital, Shanghai, China.
authors.forename: Xilu
authors.initials: X
authors.lastname: Yi
authors.affiliation: Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Mengjuan
authors.initials: M
authors.lastname: Xue
authors.affiliation: Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Shunmei
authors.initials: S
authors.lastname: He
authors.affiliation: Institute of Radiation Medicine, Fudan University, Shanghai, China.
authors.forename: Guoying
authors.initials: G
authors.lastname: Zhu
authors.affiliation: Institute of Radiation Medicine, Fudan University, Shanghai, China. Electronic address: hfwang@shmu.edu.cn.
authors.forename: Hongfu
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D050778:NFATC Transcription Factors / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D053245:RANK Ligand / Q000494:pharmacology; D012717:Sesquiterpenes / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D004365:Drugs, Chinese Herbal; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D053245:RANK Ligand; D012717:Sesquiterpenes; D018808:Transcription Factor AP-1; D000841:Anisomycin; C022801:curcumol
keywords: Antiresorptive agent; Curcumol; JNK; Osteoclast; RANKL