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Chicago sky blue 6B (CSB6B), an allosteric inhibitor of macrophage migration inhibitory factor (MIF), suppresses osteoclastogenesis and promotes osteogenesis through the inhibition of the NF-κB signaling pathway.
Jin, Kangtao; Zheng, Lin; Ye, Lin; Xie, Ziang; Gao, Jiawei; Lou, Chao; Pan, Wenzheng; Pan, Bin; Liu, Shijie; Chen, Zhenzhong; He, Dengwei.
Afiliación
  • Jin K; Department of Orthopedics, Affiliated Lishui Hospital of Zhejiang University/the Fifth Affiliated Hospital of Wenzhou Medical University/Lishui Central Hospital, Lishui, China.
  • Zheng L; Department of Orthopedics, Affiliated Lishui Hospital of Zhejiang University/the Fifth Affiliated Hospital of Wenzhou Medical University/Lishui Central Hospital, Lishui, China; Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China; Key
  • Ye L; Department of Orthopedics, Affiliated Lishui Hospital of Zhejiang University/the Fifth Affiliated Hospital of Wenzhou Medical University/Lishui Central Hospital, Lishui, China.
  • Xie Z; Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China; Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province, Hangzhou, China.
  • Gao J; Department of Orthopedics, Affiliated Lishui Hospital of Zhejiang University/the Fifth Affiliated Hospital of Wenzhou Medical University/Lishui Central Hospital, Lishui, China.
  • Lou C; Department of Orthopedics, Affiliated Lishui Hospital of Zhejiang University/the Fifth Affiliated Hospital of Wenzhou Medical University/Lishui Central Hospital, Lishui, China.
  • Pan W; Department of Orthopedics, Affiliated Lishui Hospital of Zhejiang University/the Fifth Affiliated Hospital of Wenzhou Medical University/Lishui Central Hospital, Lishui, China.
  • Pan B; Department of Orthopedics, Affiliated Lishui Hospital of Zhejiang University/the Fifth Affiliated Hospital of Wenzhou Medical University/Lishui Central Hospital, Lishui, China.
  • Liu S; Department of Orthopedics, Affiliated Lishui Hospital of Zhejiang University/the Fifth Affiliated Hospital of Wenzhou Medical University/Lishui Central Hospital, Lishui, China.
  • Chen Z; Department of Orthopedics, Affiliated Lishui Hospital of Zhejiang University/the Fifth Affiliated Hospital of Wenzhou Medical University/Lishui Central Hospital, Lishui, China; Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province, Hangzho
  • He D; Department of Orthopedics, Affiliated Lishui Hospital of Zhejiang University/the Fifth Affiliated Hospital of Wenzhou Medical University/Lishui Central Hospital, Lishui, China. Electronic address: hedw120@zju.edu.cn.
Biochem Pharmacol ; 192: 114734, 2021 10.
Article en En | MEDLINE | ID: mdl-34411569
Macrophage migration inhibitory factor (MIF) is a pleiotropic pro-inflammatory mediator involved in various pathophysiological and inflammatory states. Accumulating line of evidence suggests a role for MIF in regulating bone metabolism and therefore a prime candidate for therapeutic targeting. In this study, we showed that Chicago sky blue 6B (CSB6B) suppresses RANKL-induced osteoclast and bone resorption in vitro via the inhibition of NF-κB signaling activation and promoting proteasome-mediated degradation of MIF. Consequently, the induction of NFATc1 was impaired resulting in downregulation of NFATc1-responsive osteoclast genes. We also demonstrated that CSB6B treatment enhanced primary calvarial osteoblast differentiation and bone mineralization in vitro via the suppression of NF-κB activation and upregulation of Runx expression. Using two murine models of osteolytic bone disorders, we further showed that administration of CSB6B protected mice against pathological inflammatoryc calvarial bone destruction induced by titanium particles mice as well as estrogen-deficiency induced bone loss as a result of ovariectomy. Together, as an MIF inhibitor, CSB6B can inhibit osteoclast differentiation and bone resorption function and enhance the mineralization of osteoblasts through the inhibition of NF-κB pathway. MIF is a prime target for therapeutic targeting for the treatment of osteolytic bone disorders and the MIF inhibitor CSB6B could be potential anti-osteoporosis drug.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteoclastos / Osteogénesis / Azul de Tripano / Transducción de Señal / FN-kappa B / Factores Inhibidores de la Migración de Macrófagos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Biochem Pharmacol Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteoclastos / Osteogénesis / Azul de Tripano / Transducción de Señal / FN-kappa B / Factores Inhibidores de la Migración de Macrófagos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Biochem Pharmacol Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido