title: Salicortin inhibits osteoclast differentiation and bone resorption by down-regulating JNK and NF-κB/NFATc1 signaling pathways.
abstract: Receptor activator of nuclear factor (NF)-κB ligand (RANKL)-activated signaling is essential for osteoclast differentiation, activation, and survival. Salicortin is a phenolic glycoside that has been isolated from many plants such as Populus and Salix species, and has been shown to have anti-amnesic and anti-adipogenic effects. In this study, we investigated the effect of salicortin on RANKL-induced osteoclasts formation, bone resorption, and activation of osteoclast-related signaling pathways. Salicortin suppressed RANKL-induced osteoclastogenesis in bone marrow macrophage cultures in a dose-dependent manner, and inhibited osteoclastic bone resorption activity without any cytotoxicity. Salicortin inhibited RANKL-induced c-Jun N-terminal kinase and NF-κB activation, concomitant with retarded IκBα phosphorylation and inhibition of p65 nuclear translocation, leading to impaired transcription of nuclear factor of activated T cells c1 (NFATc1) and expression of osteoclastic-specific genes. Taken together, our findings demonstrate that salicortin inhibits NF-κB and NFATc1 activation, leading to attenuation of osteoclastogenesis and bone resorption. Thus, salicortin may be of interest in developments of treatment for osteoclast related diseases.
authors.affiliation: Department of Orthopaedics, PLA General Hospital, Beijing 100853, PR China.
authors.forename: Shaobo
authors.initials: S
authors.lastname: Nie
authors.affiliation: Department of Orthopaedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, PRChina.
authors.forename: Jiawei
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Orthopaedics, Changle County Hospital of Traditional Chinese Medicine, Weifang 262400, PR China.
authors.forename: Chenghua
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, PRChina.
authors.forename: Chen
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Orthopaedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, PRChina. Electronic address: ming_li4717@sina.com.
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, PRChina. Electronic address: ydg163@126.com.
authors.forename: Degang
authors.initials: D
authors.lastname: Yu
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D005960:Glucosides / Q000008:administration & dosage*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000378:metabolism*; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D013977:Tibia
chemical_list: D005960:Glucosides; D016328:NF-kappa B; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; C113068:salicortin
keywords: JNK; NF-κB/NFATc1; Osteoclastogenesis; Salicortin