Gossypol Promotes Bone Formation in Ovariectomy-Induced Osteoporosis through Regulating Cell Apoptosis
Osteoporosis is among the most common forms of age-related diseases, especially for females, which has been a grave public health problem. Drug therapies have shown promising outcomes to promote bone formation and bone density. This study identified a novel potential drug, gossypol, for the treatmen...
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| Veröffentlicht in: | BioMed research international 2018-01, Vol.2018 (2018), p.1-9 |
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| creator | Zhao, Hong Li, Zheng Liu, Xiangyang Liu, Hongzhe Chen, Chong Liang, Jinqian Hu, Jianhua |
| description | Osteoporosis is among the most common forms of age-related diseases, especially for females, which has been a grave public health problem. Drug therapies have shown promising outcomes to promote bone formation and bone density. This study identified a novel potential drug, gossypol, for the treatment of osteoporosis. Treatments of ovariectomy-induced osteoporosis mice with gossypol significantly increased serum osteocalcin and osteoprotegerin (OPG) levels; meanwhile they decreased serum RANKL levels. Microcomputed tomography (microCT) analysis showed that treatment of gossypol improved bone density and strength and decreased bone postyield displacement for both medullar and cortical bones. In vitro experiments also showed that gossypol increased cell viability in a time- and dose-dependent manner. Furthermore, incubation of the osteoblast MC3T3-E1 cells with gossypol inhibited cell apoptosis through intrinsic apoptotic pathway as evidenced by the Annexin V/PI assay, TUNEL assay, biochemical analysis, and western blot assays. Moreover, the classical Wnt/β-catenin signaling pathway was found to be regulated by gossypol treatments. Inhibition of Wnt/β-catenin signaling reversed the prevention effects of gossypol in osteoporosis. Our findings provided novel clues for the treatment of osteoporosis in clinic. |
| doi_str_mv | 10.1155/2018/3635485 |
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Drug therapies have shown promising outcomes to promote bone formation and bone density. This study identified a novel potential drug, gossypol, for the treatment of osteoporosis. Treatments of ovariectomy-induced osteoporosis mice with gossypol significantly increased serum osteocalcin and osteoprotegerin (OPG) levels; meanwhile they decreased serum RANKL levels. Microcomputed tomography (microCT) analysis showed that treatment of gossypol improved bone density and strength and decreased bone postyield displacement for both medullar and cortical bones. In vitro experiments also showed that gossypol increased cell viability in a time- and dose-dependent manner. Furthermore, incubation of the osteoblast MC3T3-E1 cells with gossypol inhibited cell apoptosis through intrinsic apoptotic pathway as evidenced by the Annexin V/PI assay, TUNEL assay, biochemical analysis, and western blot assays. Moreover, the classical Wnt/β-catenin signaling pathway was found to be regulated by gossypol treatments. Inhibition of Wnt/β-catenin signaling reversed the prevention effects of gossypol in osteoporosis. Our findings provided novel clues for the treatment of osteoporosis in clinic.</description><identifier>ISSN: 2314-6133</identifier><identifier>EISSN: 2314-6141</identifier><identifier>DOI: 10.1155/2018/3635485</identifier><identifier>PMID: 30643801</identifier><language>eng</language><publisher>Cairo, Egypt: Hindawi Publishing Corporation</publisher><subject>Age ; Analysis ; Annexin V ; Apoptosis ; Assaying ; Biochemical analysis ; Biocompatibility ; Biomedical materials ; Bone density ; Bone growth ; Bones ; Computed tomography ; Dehydrogenases ; Drug dosages ; Females ; Fluorides ; Fractures ; Gossypol ; Histology ; Incubation ; Medicine ; Osteocalcin ; Osteogenesis ; Osteoporosis ; Osteoprotegerin ; Ovariectomy ; Oxidative stress ; Physiology ; Public health ; Signal transduction ; Signaling ; Time dependence ; TRANCE protein ; Wnt protein ; β-Catenin</subject><ispartof>BioMed research international, 2018-01, Vol.2018 (2018), p.1-9</ispartof><rights>Copyright © 2018 Jinqian Liang et al.</rights><rights>COPYRIGHT 2018 John Wiley & Sons, Inc.</rights><rights>Copyright © 2018 Jinqian Liang et al. This is an open access article distributed under the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. https://creativecommons.org/licenses/by/4.0</rights><rights>Copyright © 2018 Jinqian Liang et al. 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c499t-c5ad88c4456dee1f09d748ad493b5971b4067fd9853da09495e11a319bb71cd23</citedby><cites>FETCH-LOGICAL-c499t-c5ad88c4456dee1f09d748ad493b5971b4067fd9853da09495e11a319bb71cd23</cites><orcidid>0000-0003-0801-2017 ; 0000-0001-5698-9389</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6311247/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6311247/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30643801$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Aliev, Gjumrakch</contributor><contributor>Gjumrakch Aliev</contributor><creatorcontrib>Zhao, Hong</creatorcontrib><creatorcontrib>Li, Zheng</creatorcontrib><creatorcontrib>Liu, Xiangyang</creatorcontrib><creatorcontrib>Liu, Hongzhe</creatorcontrib><creatorcontrib>Chen, Chong</creatorcontrib><creatorcontrib>Liang, Jinqian</creatorcontrib><creatorcontrib>Hu, Jianhua</creatorcontrib><title>Gossypol Promotes Bone Formation in Ovariectomy-Induced Osteoporosis through Regulating Cell Apoptosis</title><title>BioMed research international</title><addtitle>Biomed Res Int</addtitle><description>Osteoporosis is among the most common forms of age-related diseases, especially for females, which has been a grave public health problem. Drug therapies have shown promising outcomes to promote bone formation and bone density. This study identified a novel potential drug, gossypol, for the treatment of osteoporosis. Treatments of ovariectomy-induced osteoporosis mice with gossypol significantly increased serum osteocalcin and osteoprotegerin (OPG) levels; meanwhile they decreased serum RANKL levels. Microcomputed tomography (microCT) analysis showed that treatment of gossypol improved bone density and strength and decreased bone postyield displacement for both medullar and cortical bones. In vitro experiments also showed that gossypol increased cell viability in a time- and dose-dependent manner. Furthermore, incubation of the osteoblast MC3T3-E1 cells with gossypol inhibited cell apoptosis through intrinsic apoptotic pathway as evidenced by the Annexin V/PI assay, TUNEL assay, biochemical analysis, and western blot assays. Moreover, the classical Wnt/β-catenin signaling pathway was found to be regulated by gossypol treatments. Inhibition of Wnt/β-catenin signaling reversed the prevention effects of gossypol in osteoporosis. Our findings provided novel clues for the treatment of osteoporosis in clinic.</description><subject>Age</subject><subject>Analysis</subject><subject>Annexin V</subject><subject>Apoptosis</subject><subject>Assaying</subject><subject>Biochemical analysis</subject><subject>Biocompatibility</subject><subject>Biomedical materials</subject><subject>Bone density</subject><subject>Bone growth</subject><subject>Bones</subject><subject>Computed tomography</subject><subject>Dehydrogenases</subject><subject>Drug dosages</subject><subject>Females</subject><subject>Fluorides</subject><subject>Fractures</subject><subject>Gossypol</subject><subject>Histology</subject><subject>Incubation</subject><subject>Medicine</subject><subject>Osteocalcin</subject><subject>Osteogenesis</subject><subject>Osteoporosis</subject><subject>Osteoprotegerin</subject><subject>Ovariectomy</subject><subject>Oxidative stress</subject><subject>Physiology</subject><subject>Public health</subject><subject>Signal 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Promotes Bone Formation in Ovariectomy-Induced Osteoporosis through Regulating Cell Apoptosis</title><author>Zhao, Hong ; Li, Zheng ; Liu, Xiangyang ; Liu, Hongzhe ; Chen, Chong ; Liang, Jinqian ; Hu, Jianhua</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c499t-c5ad88c4456dee1f09d748ad493b5971b4067fd9853da09495e11a319bb71cd23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Age</topic><topic>Analysis</topic><topic>Annexin V</topic><topic>Apoptosis</topic><topic>Assaying</topic><topic>Biochemical analysis</topic><topic>Biocompatibility</topic><topic>Biomedical materials</topic><topic>Bone density</topic><topic>Bone growth</topic><topic>Bones</topic><topic>Computed tomography</topic><topic>Dehydrogenases</topic><topic>Drug dosages</topic><topic>Females</topic><topic>Fluorides</topic><topic>Fractures</topic><topic>Gossypol</topic><topic>Histology</topic><topic>Incubation</topic><topic>Medicine</topic><topic>Osteocalcin</topic><topic>Osteogenesis</topic><topic>Osteoporosis</topic><topic>Osteoprotegerin</topic><topic>Ovariectomy</topic><topic>Oxidative stress</topic><topic>Physiology</topic><topic>Public health</topic><topic>Signal transduction</topic><topic>Signaling</topic><topic>Time dependence</topic><topic>TRANCE protein</topic><topic>Wnt protein</topic><topic>β-Catenin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhao, Hong</creatorcontrib><creatorcontrib>Li, Zheng</creatorcontrib><creatorcontrib>Liu, Xiangyang</creatorcontrib><creatorcontrib>Liu, Hongzhe</creatorcontrib><creatorcontrib>Chen, Chong</creatorcontrib><creatorcontrib>Liang, Jinqian</creatorcontrib><creatorcontrib>Hu, Jianhua</creatorcontrib><collection>الدوريات العلمية والإحصائية - e-Marefa 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international</jtitle><addtitle>Biomed Res Int</addtitle><date>2018-01-01</date><risdate>2018</risdate><volume>2018</volume><issue>2018</issue><spage>1</spage><epage>9</epage><pages>1-9</pages><issn>2314-6133</issn><eissn>2314-6141</eissn><abstract>Osteoporosis is among the most common forms of age-related diseases, especially for females, which has been a grave public health problem. Drug therapies have shown promising outcomes to promote bone formation and bone density. This study identified a novel potential drug, gossypol, for the treatment of osteoporosis. Treatments of ovariectomy-induced osteoporosis mice with gossypol significantly increased serum osteocalcin and osteoprotegerin (OPG) levels; meanwhile they decreased serum RANKL levels. Microcomputed tomography (microCT) analysis showed that treatment of gossypol improved bone density and strength and decreased bone postyield displacement for both medullar and cortical bones. In vitro experiments also showed that gossypol increased cell viability in a time- and dose-dependent manner. Furthermore, incubation of the osteoblast MC3T3-E1 cells with gossypol inhibited cell apoptosis through intrinsic apoptotic pathway as evidenced by the Annexin V/PI assay, TUNEL assay, biochemical analysis, and western blot assays. Moreover, the classical Wnt/β-catenin signaling pathway was found to be regulated by gossypol treatments. Inhibition of Wnt/β-catenin signaling reversed the prevention effects of gossypol in osteoporosis. Our findings provided novel clues for the treatment of osteoporosis in clinic.</abstract><cop>Cairo, Egypt</cop><pub>Hindawi Publishing Corporation</pub><pmid>30643801</pmid><doi>10.1155/2018/3635485</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0003-0801-2017</orcidid><orcidid>https://orcid.org/0000-0001-5698-9389</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Age Analysis Annexin V Apoptosis Assaying Biochemical analysis Biocompatibility Biomedical materials Bone density Bone growth Bones Computed tomography Dehydrogenases Drug dosages Females Fluorides Fractures Gossypol Histology Incubation Medicine Osteocalcin Osteogenesis Osteoporosis Osteoprotegerin Ovariectomy Oxidative stress Physiology Public health Signal transduction Signaling Time dependence TRANCE protein Wnt protein β-Catenin |
| title | Gossypol Promotes Bone Formation in Ovariectomy-Induced Osteoporosis through Regulating Cell Apoptosis |
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