Wnt16 Is Associated with Age-Related Bone Loss and Estrogen Withdrawal in Murine Bone
Genome Wide Association Studies suggest that Wnt16 is an important contributor to the mechanisms controlling bone mineral density, cortical thickness, bone strength and ultimately fracture risk. Wnt16 acts on osteoblasts and osteoclasts and, in cortical bone, is predominantly derived from osteoblast...
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| description | Genome Wide Association Studies suggest that Wnt16 is an important contributor to the mechanisms controlling bone mineral density, cortical thickness, bone strength and ultimately fracture risk. Wnt16 acts on osteoblasts and osteoclasts and, in cortical bone, is predominantly derived from osteoblasts. This led us to hypothesize that low bone mass would be associated with low levels of Wnt16 expression and that Wnt16 expression would be increased by anabolic factors, including mechanical loading. We therefore investigated Wnt16 expression in the context of ageing, mechanical loading and unloading, estrogen deficiency and replacement, and estrogen receptor α (ERα) depletion. Quantitative real time PCR showed that Wnt16 mRNA expression was lower in cortical bone and marrow of aged compared to young female mice. Neither increased nor decreased (by disuse) mechanical loading altered Wnt16 expression in young female mice, although Wnt16 expression was decreased following ovariectomy. Both 17β-estradiol and the Selective Estrogen Receptor Modulator Tamoxifen increased Wnt16 expression relative to ovariectomy. Wnt16 and ERβ expression were increased in female ERα-/- mice when compared to Wild Type. We also addressed potential effects of gender on Wnt16 expression and while the expression was lower in the cortical bone of aged males as in females, it was higher in male bone marrow of aged mice compared to young. In the kidney, which we used as a non-bone reference tissue, Wnt16 expression was unaffected by age in either males or females. In summary, age, and its associated bone loss, is associated with low levels of Wnt16 expression whereas bone loss associated with disuse has no effect on Wnt16 expression. In the artificially loaded mouse tibia we observed no loading-related up-regulation of Wnt16 expression but provide evidence that its expression is influenced by estrogen receptor signaling. These findings suggest that while Wnt16 is not an obligatory contributor to regulation of bone mass per se, it potentially plays a role in influencing pathways associated with regulation of bone mass during ageing and estrogen withdrawal. |
| doi_str_mv | 10.1371/journal.pone.0140260 |
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Wnt16 acts on osteoblasts and osteoclasts and, in cortical bone, is predominantly derived from osteoblasts. This led us to hypothesize that low bone mass would be associated with low levels of Wnt16 expression and that Wnt16 expression would be increased by anabolic factors, including mechanical loading. We therefore investigated Wnt16 expression in the context of ageing, mechanical loading and unloading, estrogen deficiency and replacement, and estrogen receptor α (ERα) depletion. Quantitative real time PCR showed that Wnt16 mRNA expression was lower in cortical bone and marrow of aged compared to young female mice. Neither increased nor decreased (by disuse) mechanical loading altered Wnt16 expression in young female mice, although Wnt16 expression was decreased following ovariectomy. Both 17β-estradiol and the Selective Estrogen Receptor Modulator Tamoxifen increased Wnt16 expression relative to ovariectomy. Wnt16 and ERβ expression were increased in female ERα-/- mice when compared to Wild Type. We also addressed potential effects of gender on Wnt16 expression and while the expression was lower in the cortical bone of aged males as in females, it was higher in male bone marrow of aged mice compared to young. In the kidney, which we used as a non-bone reference tissue, Wnt16 expression was unaffected by age in either males or females. In summary, age, and its associated bone loss, is associated with low levels of Wnt16 expression whereas bone loss associated with disuse has no effect on Wnt16 expression. In the artificially loaded mouse tibia we observed no loading-related up-regulation of Wnt16 expression but provide evidence that its expression is influenced by estrogen receptor signaling. These findings suggest that while Wnt16 is not an obligatory contributor to regulation of bone mass per se, it potentially plays a role in influencing pathways associated with regulation of bone mass during ageing and estrogen withdrawal.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0140260</identifier><identifier>PMID: 26451596</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>17β-Estradiol ; Age ; Aging ; Aging - metabolism ; Animals ; Biocompatibility ; Biomedical materials ; Bone (cortical) ; Bone density ; Bone loss ; Bone marrow ; Bone mass ; Bone mineral density ; Bone strength ; Cell and Molecular Biology ; Cell- och molekylärbiologi ; Cooperation ; CORTICAL BONE ; Estrogen Receptor alpha - metabolism ; Estrogens ; Estrogens - metabolism ; Estrogens - pharmacology ; Female ; FEMALE MICE ; Females ; Gene Expression Regulation - drug effects ; GENE-EXPRESSION ; Genetic aspects ; GENOME-WIDE ; Genomes ; KAPPA-B ; Kidneys ; LOAD-BEARING ; Male ; MALE-MICE ; Males ; Mechanical loading ; Mechanical properties ; Mechanical unloading ; Medical research ; Mice ; Mice, Inbred C57BL ; MINERAL DENSITY ; Mutation ; Nutrition research ; Osteoblasts ; Osteoclasts ; OSTEOGENIC ; Osteoporosis ; Osteoporosis - genetics ; Osteoporosis - metabolism ; Osteoporosis - physiopathology ; Ovariectomy ; Physiological aspects ; RECEPTOR-ALPHA ; RESPONSE ; Risk factors ; Rodents ; Sex hormones ; Tamoxifen ; Tibia ; Tibia - drug effects ; Tibia - metabolism ; Tibia - physiopathology ; Unloading ; Weight-Bearing ; Wnt proteins ; Wnt Proteins - genetics ; Wnt Proteins - metabolism</subject><ispartof>PloS one, 2015-10, Vol.10 (10), p.e0140260-e0140260</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Todd et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Todd et al 2015 Todd et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c730t-20adca467bb0d95fef285de8a9392b0831ed981380396ee9859687ed4cddb5803</citedby><cites>FETCH-LOGICAL-c730t-20adca467bb0d95fef285de8a9392b0831ed981380396ee9859687ed4cddb5803</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599960/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599960/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26451596$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://gup.ub.gu.se/publication/225681$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><contributor>Vanacker, Jean-Marc</contributor><creatorcontrib>Todd, Henry</creatorcontrib><creatorcontrib>Galea, Gabriel L</creatorcontrib><creatorcontrib>Meakin, Lee B</creatorcontrib><creatorcontrib>Delisser, Peter J</creatorcontrib><creatorcontrib>Lanyon, Lance E</creatorcontrib><creatorcontrib>Windahl, Sara H</creatorcontrib><creatorcontrib>Price, Joanna S</creatorcontrib><title>Wnt16 Is Associated with Age-Related Bone Loss and Estrogen Withdrawal in Murine Bone</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Genome Wide Association Studies suggest that Wnt16 is an important contributor to the mechanisms controlling bone mineral density, cortical thickness, bone strength and ultimately fracture risk. Wnt16 acts on osteoblasts and osteoclasts and, in cortical bone, is predominantly derived from osteoblasts. This led us to hypothesize that low bone mass would be associated with low levels of Wnt16 expression and that Wnt16 expression would be increased by anabolic factors, including mechanical loading. We therefore investigated Wnt16 expression in the context of ageing, mechanical loading and unloading, estrogen deficiency and replacement, and estrogen receptor α (ERα) depletion. Quantitative real time PCR showed that Wnt16 mRNA expression was lower in cortical bone and marrow of aged compared to young female mice. Neither increased nor decreased (by disuse) mechanical loading altered Wnt16 expression in young female mice, although Wnt16 expression was decreased following ovariectomy. Both 17β-estradiol and the Selective Estrogen Receptor Modulator Tamoxifen increased Wnt16 expression relative to ovariectomy. Wnt16 and ERβ expression were increased in female ERα-/- mice when compared to Wild Type. We also addressed potential effects of gender on Wnt16 expression and while the expression was lower in the cortical bone of aged males as in females, it was higher in male bone marrow of aged mice compared to young. In the kidney, which we used as a non-bone reference tissue, Wnt16 expression was unaffected by age in either males or females. In summary, age, and its associated bone loss, is associated with low levels of Wnt16 expression whereas bone loss associated with disuse has no effect on Wnt16 expression. In the artificially loaded mouse tibia we observed no loading-related up-regulation of Wnt16 expression but provide evidence that its expression is influenced by estrogen receptor signaling. These findings suggest that while Wnt16 is not an obligatory contributor to regulation of bone mass per se, it potentially plays a role in influencing pathways associated with regulation of bone mass during ageing and estrogen withdrawal.</description><subject>17β-Estradiol</subject><subject>Age</subject><subject>Aging</subject><subject>Aging - metabolism</subject><subject>Animals</subject><subject>Biocompatibility</subject><subject>Biomedical materials</subject><subject>Bone (cortical)</subject><subject>Bone density</subject><subject>Bone loss</subject><subject>Bone marrow</subject><subject>Bone mass</subject><subject>Bone mineral density</subject><subject>Bone strength</subject><subject>Cell and Molecular Biology</subject><subject>Cell- och molekylärbiologi</subject><subject>Cooperation</subject><subject>CORTICAL BONE</subject><subject>Estrogen Receptor alpha - metabolism</subject><subject>Estrogens</subject><subject>Estrogens - metabolism</subject><subject>Estrogens - pharmacology</subject><subject>Female</subject><subject>FEMALE MICE</subject><subject>Females</subject><subject>Gene Expression Regulation - drug effects</subject><subject>GENE-EXPRESSION</subject><subject>Genetic aspects</subject><subject>GENOME-WIDE</subject><subject>Genomes</subject><subject>KAPPA-B</subject><subject>Kidneys</subject><subject>LOAD-BEARING</subject><subject>Male</subject><subject>MALE-MICE</subject><subject>Males</subject><subject>Mechanical loading</subject><subject>Mechanical properties</subject><subject>Mechanical unloading</subject><subject>Medical research</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>MINERAL DENSITY</subject><subject>Mutation</subject><subject>Nutrition research</subject><subject>Osteoblasts</subject><subject>Osteoclasts</subject><subject>OSTEOGENIC</subject><subject>Osteoporosis</subject><subject>Osteoporosis - genetics</subject><subject>Osteoporosis - metabolism</subject><subject>Osteoporosis - physiopathology</subject><subject>Ovariectomy</subject><subject>Physiological aspects</subject><subject>RECEPTOR-ALPHA</subject><subject>RESPONSE</subject><subject>Risk factors</subject><subject>Rodents</subject><subject>Sex hormones</subject><subject>Tamoxifen</subject><subject>Tibia</subject><subject>Tibia - drug effects</subject><subject>Tibia - metabolism</subject><subject>Tibia - physiopathology</subject><subject>Unloading</subject><subject>Weight-Bearing</subject><subject>Wnt proteins</subject><subject>Wnt Proteins - genetics</subject><subject>Wnt Proteins - metabolism</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk1Fv0zAQxyMEYqPwDRBEQkLwkGLHiWO_IJVpQKWiSYOxR8uJL6mnNO5sh8K3x2mzqUF7QH6I9c_v_nc--6LoJUZzTAr84cb0tpPtfGs6mCOcoZSiR9Ep5iRNaIrI46P9SfTMuRuEcsIofRqdpDTLcc7paXR13XlM46WLF86ZSksPKt5pv44XDSSX0O6FTyFHvDLOxbJT8bnz1jTQxdeBU1buZBvrLv7WWx2wgX0ePall6-DF-J1FV5_Pf5x9TVYXX5Zni1VSFQT5JEVSVTKjRVkixfMa6pTlCpjkhKclYgSD4gwThginAJyFklkBKquUKvOgzqLXB99ta5wYO-IELlKMM4bQQCwPhDLyRmyt3kj7RxipxV4wthHSel21IDAvsCIUFxjxrAylsKwkDJcIB7OykMErOXi5HWz7cuLW9FsRpKYXDkSa5jSUPYs-jtX15QZUBZ23sp2ETf90ei0a80tkOeecDsW_Gw2sue3BebHRroK2lR2Yfn_OFDOK6ZDrzT_ow90YqUaGA-uuNiFvNZiKRUZweBIZHqj5A1RYCja6Ctdb66BPAt5PAgLj4bdvZO-cWH6__H_24ueUfXvErkG2fu1M23ttOjcFswNY2fBILdT3TcZIDNNy1w0xTIsYpyWEvTq-oPugu_EgfwEFxAxL</recordid><startdate>20151009</startdate><enddate>20151009</enddate><creator>Todd, Henry</creator><creator>Galea, Gabriel L</creator><creator>Meakin, Lee B</creator><creator>Delisser, Peter J</creator><creator>Lanyon, Lance E</creator><creator>Windahl, Sara H</creator><creator>Price, Joanna S</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>F1U</scope><scope>DOA</scope></search><sort><creationdate>20151009</creationdate><title>Wnt16 Is Associated with Age-Related Bone Loss and Estrogen Withdrawal in Murine Bone</title><author>Todd, Henry ; Galea, Gabriel L ; Meakin, Lee B ; Delisser, Peter J ; Lanyon, Lance E ; Windahl, Sara H ; Price, Joanna S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c730t-20adca467bb0d95fef285de8a9392b0831ed981380396ee9859687ed4cddb5803</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>17β-Estradiol</topic><topic>Age</topic><topic>Aging</topic><topic>Aging - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Göteborgs universitet</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Todd, Henry</au><au>Galea, Gabriel L</au><au>Meakin, Lee B</au><au>Delisser, Peter J</au><au>Lanyon, Lance E</au><au>Windahl, Sara H</au><au>Price, Joanna S</au><au>Vanacker, Jean-Marc</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Wnt16 Is Associated with Age-Related Bone Loss and Estrogen Withdrawal in Murine Bone</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-10-09</date><risdate>2015</risdate><volume>10</volume><issue>10</issue><spage>e0140260</spage><epage>e0140260</epage><pages>e0140260-e0140260</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Genome Wide Association Studies suggest that Wnt16 is an important contributor to the mechanisms controlling bone mineral density, cortical thickness, bone strength and ultimately fracture risk. Wnt16 acts on osteoblasts and osteoclasts and, in cortical bone, is predominantly derived from osteoblasts. This led us to hypothesize that low bone mass would be associated with low levels of Wnt16 expression and that Wnt16 expression would be increased by anabolic factors, including mechanical loading. We therefore investigated Wnt16 expression in the context of ageing, mechanical loading and unloading, estrogen deficiency and replacement, and estrogen receptor α (ERα) depletion. Quantitative real time PCR showed that Wnt16 mRNA expression was lower in cortical bone and marrow of aged compared to young female mice. Neither increased nor decreased (by disuse) mechanical loading altered Wnt16 expression in young female mice, although Wnt16 expression was decreased following ovariectomy. Both 17β-estradiol and the Selective Estrogen Receptor Modulator Tamoxifen increased Wnt16 expression relative to ovariectomy. Wnt16 and ERβ expression were increased in female ERα-/- mice when compared to Wild Type. We also addressed potential effects of gender on Wnt16 expression and while the expression was lower in the cortical bone of aged males as in females, it was higher in male bone marrow of aged mice compared to young. In the kidney, which we used as a non-bone reference tissue, Wnt16 expression was unaffected by age in either males or females. In summary, age, and its associated bone loss, is associated with low levels of Wnt16 expression whereas bone loss associated with disuse has no effect on Wnt16 expression. In the artificially loaded mouse tibia we observed no loading-related up-regulation of Wnt16 expression but provide evidence that its expression is influenced by estrogen receptor signaling. These findings suggest that while Wnt16 is not an obligatory contributor to regulation of bone mass per se, it potentially plays a role in influencing pathways associated with regulation of bone mass during ageing and estrogen withdrawal.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26451596</pmid><doi>10.1371/journal.pone.0140260</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2015-10, Vol.10 (10), p.e0140260-e0140260 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1721148000 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | 17β-Estradiol Age Aging Aging - metabolism Animals Biocompatibility Biomedical materials Bone (cortical) Bone density Bone loss Bone marrow Bone mass Bone mineral density Bone strength Cell and Molecular Biology Cell- och molekylärbiologi Cooperation CORTICAL BONE Estrogen Receptor alpha - metabolism Estrogens Estrogens - metabolism Estrogens - pharmacology Female FEMALE MICE Females Gene Expression Regulation - drug effects GENE-EXPRESSION Genetic aspects GENOME-WIDE Genomes KAPPA-B Kidneys LOAD-BEARING Male MALE-MICE Males Mechanical loading Mechanical properties Mechanical unloading Medical research Mice Mice, Inbred C57BL MINERAL DENSITY Mutation Nutrition research Osteoblasts Osteoclasts OSTEOGENIC Osteoporosis Osteoporosis - genetics Osteoporosis - metabolism Osteoporosis - physiopathology Ovariectomy Physiological aspects RECEPTOR-ALPHA RESPONSE Risk factors Rodents Sex hormones Tamoxifen Tibia Tibia - drug effects Tibia - metabolism Tibia - physiopathology Unloading Weight-Bearing Wnt proteins Wnt Proteins - genetics Wnt Proteins - metabolism |
| title | Wnt16 Is Associated with Age-Related Bone Loss and Estrogen Withdrawal in Murine Bone |
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