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Gossypol Promotes Wnt/β-Catenin Signaling through WIF1 in Ovariectomy-Induced Osteoporosis

Osteoporosis is one of the most frequent diseases related with age. Previously, we have reported a novel potential drug, gossypol, for the treatment of osteoporosis through its regulation of Wnt/β-catenin signaling. This study aims to identify the detailed mechanism of gossypol in human osteoporosis...

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Detalles Bibliográficos
Autores principales: Liang, Jinqian, Chen, Chong, Liu, Hongzhe, Liu, Xiangyang, Zhao, Hong, Hu, Jianhua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6500658/
https://www.ncbi.nlm.nih.gov/pubmed/31139657
http://dx.doi.org/10.1155/2019/8745487
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author Liang, Jinqian
Chen, Chong
Liu, Hongzhe
Liu, Xiangyang
Zhao, Hong
Hu, Jianhua
author_facet Liang, Jinqian
Chen, Chong
Liu, Hongzhe
Liu, Xiangyang
Zhao, Hong
Hu, Jianhua
author_sort Liang, Jinqian
collection PubMed
description Osteoporosis is one of the most frequent diseases related with age. Previously, we have reported a novel potential drug, gossypol, for the treatment of osteoporosis through its regulation of Wnt/β-catenin signaling. This study aims to identify the detailed mechanism of gossypol in human osteoporosis. Mice injected with gossypol were subjected for RNA-seq analysis and the transcription level of WIF1 was shown to be decreased dramatically in gossypol-treated mice, which was further confirmed by qRT-PCR and western blot analysis. Luciferase reporter assay showed gossypol inhibited the activity of WIF1 and the methylation of WIF1 was significantly upregulated, evidenced by ChIP assay. Cell viability assays demonstrated that gossypol promoted cell proliferation while cotreatment with WIF1 expressing plasmid reversed the effect in a dose- and time-dependent manner. Similarly, cell apoptotic assays and TUNEL assays showed gossypol suppressed cell apoptosis, which was revised by WIF1 overexpression. The mouse model suggested gossypol injection ameliorated osteoporosis, while coinjection of AAV5-WIF1 eliminated the protection effects of gossypol, as evidenced by H&E staining, serum osteocalcin level, serum OPG level, serum RANKL level, bone density, ultimate strength, and postyield displacement. This study is a supplement to the former publication, which reinforced the protection effect of gossypol in human osteoporosis.
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spelling pubmed-65006582019-05-28 Gossypol Promotes Wnt/β-Catenin Signaling through WIF1 in Ovariectomy-Induced Osteoporosis Liang, Jinqian Chen, Chong Liu, Hongzhe Liu, Xiangyang Zhao, Hong Hu, Jianhua Biomed Res Int Research Article Osteoporosis is one of the most frequent diseases related with age. Previously, we have reported a novel potential drug, gossypol, for the treatment of osteoporosis through its regulation of Wnt/β-catenin signaling. This study aims to identify the detailed mechanism of gossypol in human osteoporosis. Mice injected with gossypol were subjected for RNA-seq analysis and the transcription level of WIF1 was shown to be decreased dramatically in gossypol-treated mice, which was further confirmed by qRT-PCR and western blot analysis. Luciferase reporter assay showed gossypol inhibited the activity of WIF1 and the methylation of WIF1 was significantly upregulated, evidenced by ChIP assay. Cell viability assays demonstrated that gossypol promoted cell proliferation while cotreatment with WIF1 expressing plasmid reversed the effect in a dose- and time-dependent manner. Similarly, cell apoptotic assays and TUNEL assays showed gossypol suppressed cell apoptosis, which was revised by WIF1 overexpression. The mouse model suggested gossypol injection ameliorated osteoporosis, while coinjection of AAV5-WIF1 eliminated the protection effects of gossypol, as evidenced by H&E staining, serum osteocalcin level, serum OPG level, serum RANKL level, bone density, ultimate strength, and postyield displacement. This study is a supplement to the former publication, which reinforced the protection effect of gossypol in human osteoporosis. Hindawi 2019-04-21 /pmc/articles/PMC6500658/ /pubmed/31139657 http://dx.doi.org/10.1155/2019/8745487 Text en Copyright © 2019 Jinqian Liang et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Liang, Jinqian
Chen, Chong
Liu, Hongzhe
Liu, Xiangyang
Zhao, Hong
Hu, Jianhua
Gossypol Promotes Wnt/β-Catenin Signaling through WIF1 in Ovariectomy-Induced Osteoporosis
title Gossypol Promotes Wnt/β-Catenin Signaling through WIF1 in Ovariectomy-Induced Osteoporosis
title_full Gossypol Promotes Wnt/β-Catenin Signaling through WIF1 in Ovariectomy-Induced Osteoporosis
title_fullStr Gossypol Promotes Wnt/β-Catenin Signaling through WIF1 in Ovariectomy-Induced Osteoporosis
title_full_unstemmed Gossypol Promotes Wnt/β-Catenin Signaling through WIF1 in Ovariectomy-Induced Osteoporosis
title_short Gossypol Promotes Wnt/β-Catenin Signaling through WIF1 in Ovariectomy-Induced Osteoporosis
title_sort gossypol promotes wnt/β-catenin signaling through wif1 in ovariectomy-induced osteoporosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6500658/
https://www.ncbi.nlm.nih.gov/pubmed/31139657
http://dx.doi.org/10.1155/2019/8745487
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