ReferenceID 4906
Cinchonine inhibits osteoclast differentiation by regulating TAK1 and AKT, and promotes osteogenesis
J Cell Physiol
Cinchonine (CN) has been known to exert antimalarial, antiplatelet, and antiobesity effects. It was also recently reported to inhibit transforming growth factor beta-activated kinase 1 (TAK1) and protein kinase B (AKT) t
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Record Fields
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- Reference Id
- 4906
- Evidence Id
- 21496
- Core Evidence Id
- 21496
- Source Reference Id
- 3077
- Herb2 Reference Id
- HBREF003874
- Subject Paper Key
- HBIN020637_32700766
- Pubmed Id
- 32700766
- Doi
- 10.1002/jcp.29968
- Paper Title
- Cinchonine inhibits osteoclast differentiation by regulating TAK1 and AKT, and promotes osteogenesis
- Paper Abstract
- Cinchonine (CN) has been known to exert antimalarial, antiplatelet, and antiobesity effects. It was also recently reported to inhibit transforming growth factor beta-activated kinase 1 (TAK1) and protein kinase B (AKT) through binding to tumor necrosis factor receptor-associated factor 6 (TRAF6). However, its role in bone metabolism remains largely unknown. Here, we showed that CN inhibits osteoclast differentiation with decreased expression of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), a key determinant of osteoclastogenesis. Immunoblot and quantitative real-time polymerase chain reaction analysis as well as the reporter assay revealed that CN inhibits nuclear factor-kappaB and activator protein-1 by regulating TAK1. CN also attenuated the activation of AKT, cyclic AMP response element-binding protein, and peroxisome proliferator-activated receptor-gamma coactivator 1beta (PGC1beta), an essential regulator of mitochondrial biogenesis. Collectively, these results suggested that CN may inhibit TRAF6-mediated TAK1 and AKT activation, which leads to downregulation of NFATc1 and PGC1beta resulting in the suppression of osteoclast differentiation. Interestingly, CN not only inhibited the maturation and resorption function of differentiated osteoclasts but also promoted osteoblast differentiation. Furthermore, CN protected lipopolysaccharide- and ovariectomy-induced bone destruction in mouse models, suggesting its therapeutic potential for treating inflammation-induced bone diseases and postmenopausal osteoporosis.
- Journal
- J Cell Physiol
- Publish Year
- 2021
- Experiment Subject
- mouse
- Experiment Type
- Cell Experiment
- Phenotype Related
- Inflammation-induced Bone Diseases; Tumor; Postmenopausal Osteoporosis
- Paper Title Cn
- Paper Title En
- Cinchonine inhibits osteoclast differentiation by regulating TAK1 and AKT, and promotes osteogenesis
- Bilingual Status
- semi_complete