Kanit BhukhaiKanoknetr SuksenNarumol BhummaphanKeatdamrong JanjornNatthakan ThongonDuangrat TantikanlayapornPawinee PiyachaturawatApichart SuksamrarnArthit ChairoungduaMahidol UniversityRamkhamhaeng University2018-06-112018-06-112012-10-19Journal of Biological Chemistry. Vol.287, No.43 (2012), 36168-361781083351X002192582-s2.0-84867837868https://repository.li.mahidol.ac.th/handle/20.500.14594/13590Estrogen promotes growth in many tissues by activating Wnt/β-catenin signaling. Recently, ASPP 049, a diarylheptanoid isolated from Curcuma comosa Roxb., has been identified as a phytoestrogen. This investigation determined the involvement of Wnt/β-catenin signaling in the estrogenic activity of this diaryl-heptanoid in transfected HEK 293T and in mouse preosteoblastic (MC3T3-E1) cells using a TOPflash luciferase assay and immunofluorescence. ASPP 049 rapidly activated T-cell-specific transcription factor/lymphoid enhancer binding factor-mediated transcription activity and induced β-catenin accumulation in the nucleus. Interestingly, the effects of ASPP 049 on the transcriptional activity and induction and accumulation of β-catenin protein in the nucleus of MC3T3-E1 cells were greater compared with estradiol. Activation of β-catenin in MC3T3-E1cells was inhibited by ICI 182,780, suggesting that an estrogen receptor is required. In addition, ASPP 049 induced phosphorylations at serine 473 of Akt and serine 9 of GSK-3β. Moreover, ASPP 049 also induced proliferation and expressions of Wnt target genes Axin2 and Runx2 in MC3T3-E1 cells. In addition, ASPP 049 increased alkaline phosphatase expression, and activity that was abolished by DKK-1, a blocker of the Wnt/β-catenin receptor. Taken together, these results suggest that ASPP 049 from C. comosa induced osteoblastic cell proliferation and differentiation through ERα-, Akt-, and GSK-3β-dependent activation of β-catenin signaling. Our findings provide a scientific rationale for using C. comosa as a dietary supplement to prevent bone loss in postmenopausal women. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyArticleSCOPUS10.1074/jbc.M112.344747