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It was also recently reported to inhibit transforming growth factor \u03b2\u2010activated kinase 1 (TAK1) and protein kinase B (AKT) through binding to tumor necrosis factor receptor\u2010associated 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\u2010cells, cytoplasmic 1 (NFATc1), a key determinant of osteoclastogenesis. Immunoblot and quantitative real\u2010time polymerase chain reaction analysis as well as the reporter assay revealed that CN inhibits nuclear factor\u2010\u03baB and activator protein\u20101 by regulating TAK1. CN also attenuated the activation of AKT, cyclic AMP response element\u2010binding protein, and peroxisome proliferator\u2010activated receptor\u2010\u03b3 coactivator 1\u03b2 (PGC1\u03b2), an essential regulator of mitochondrial biogenesis. Collectively, these results suggested that CN may inhibit TRAF6\u2010mediated TAK1 and AKT activation, which leads to downregulation of NFATc1 and PGC1\u03b2 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\u2010 and ovariectomy\u2010induced bone destruction in mouse models, suggesting its therapeutic potential for treating inflammation\u2010induced bone diseases and postmenopausal osteoporosis.<\/jats:p>","DOI":"10.1002\/jcp.29968","type":"journal-article","created":{"date-parts":[[2020,7,23]],"date-time":"2020-07-23T11:23:22Z","timestamp":1595503402000},"page":"1854-1865","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Cinchonine inhibits osteoclast differentiation by regulating TAK1 and AKT, and promotes osteogenesis"],"prefix":"10.1002","volume":"236","author":[{"given":"You\u2010Jin","family":"Jo","sequence":"first","affiliation":[{"name":"Department of Life Science Research Center for Cellular Homeostasis, Ewha Womans University  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye 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