Dose-dependent effects of genistein on bone homeostasis in rats' mandibular subchondral bone
Identifieur interne : 000015 ( Pmc/Corpus ); précédent : 000014; suivant : 000016Dose-dependent effects of genistein on bone homeostasis in rats' mandibular subchondral bone
Auteurs : Yong-Qi Li ; Xiang-Hui Xing ; Hui Wang ; Xi-Li Weng ; Shi-Bin Yu ; Guang-Ying DongSource :
- Acta Pharmacologica Sinica [ 1671-4083 ] ; 2011.
Abstract
To investigate the effect of genistein on bone homeostasis in mandibular subchondral bone of rats.
Female SD rats were administered with genistein (10 and 50 mg/kg) or placebo by oral gavage for 6 weeks. Then the animals were sacrificed, and histomorphology and micro-structure of mandibular condyle were examined using HE staining and micro-CT analysis, respectively. The expression levels of alkaline phosphatase (ALP), osteocalcin (OC), osteoprotegerin (OPG), the receptor activator of nuclear factor κB ligand (RANKL) and estrogen receptors (ERs) in mandibular condyle were detected using real-time PCR. Cultured osteoblasts were prepared from rat mandibular condyle for in
At both the low- and high-doses, genistein significantly increased the bone mineral density (BMD) and bone volume, and resulted in thicker subchondral trabecular bone
In rat mandibular condylar subchondral bone, low-dose genistein increases bone formation and inhibit bone resorption, while excess genistein inhibits both bone formation and resorption. The effects of genistein were predominantly mediated through ERβ.
Url:
DOI: 10.1038/aps.2011.136
PubMed: 22120966
PubMed Central: 4010271
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PMC:4010271Le document en format XML
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<author><name sortKey="Li, Yong Qi" sort="Li, Yong Qi" uniqKey="Li Y" first="Yong-Qi" last="Li">Yong-Qi Li</name>
<affiliation><nlm:aff id="aff1"><institution>Xijing Hospital, Fourth Military Medical University</institution>
, Xi'an 710032,<country>China</country>
</nlm:aff>
</affiliation>
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<author><name sortKey="Xing, Xiang Hui" sort="Xing, Xiang Hui" uniqKey="Xing X" first="Xiang-Hui" last="Xing">Xiang-Hui Xing</name>
<affiliation><nlm:aff id="aff2"><institution>School of Stomatology, Fourth Military Medical University</institution>
, Xi'an 710032,<country>China</country>
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<author><name sortKey="Wang, Hui" sort="Wang, Hui" uniqKey="Wang H" first="Hui" last="Wang">Hui Wang</name>
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, Xi'an 710032,<country>China</country>
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<author><name sortKey="Weng, Xi Li" sort="Weng, Xi Li" uniqKey="Weng X" first="Xi-Li" last="Weng">Xi-Li Weng</name>
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<author><name sortKey="Yu, Shi Bin" sort="Yu, Shi Bin" uniqKey="Yu S" first="Shi-Bin" last="Yu">Shi-Bin Yu</name>
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<author><name sortKey="Dong, Guang Ying" sort="Dong, Guang Ying" uniqKey="Dong G" first="Guang-Ying" last="Dong">Guang-Ying Dong</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Dose-dependent effects of genistein on bone homeostasis in rats' mandibular subchondral bone</title>
<author><name sortKey="Li, Yong Qi" sort="Li, Yong Qi" uniqKey="Li Y" first="Yong-Qi" last="Li">Yong-Qi Li</name>
<affiliation><nlm:aff id="aff1"><institution>Xijing Hospital, Fourth Military Medical University</institution>
, Xi'an 710032,<country>China</country>
</nlm:aff>
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<author><name sortKey="Xing, Xiang Hui" sort="Xing, Xiang Hui" uniqKey="Xing X" first="Xiang-Hui" last="Xing">Xiang-Hui Xing</name>
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, Xi'an 710032,<country>China</country>
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<author><name sortKey="Wang, Hui" sort="Wang, Hui" uniqKey="Wang H" first="Hui" last="Wang">Hui Wang</name>
<affiliation><nlm:aff id="aff2"><institution>School of Stomatology, Fourth Military Medical University</institution>
, Xi'an 710032,<country>China</country>
</nlm:aff>
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<author><name sortKey="Weng, Xi Li" sort="Weng, Xi Li" uniqKey="Weng X" first="Xi-Li" last="Weng">Xi-Li Weng</name>
<affiliation><nlm:aff id="aff2"><institution>School of Stomatology, Fourth Military Medical University</institution>
, Xi'an 710032,<country>China</country>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Yu, Shi Bin" sort="Yu, Shi Bin" uniqKey="Yu S" first="Shi-Bin" last="Yu">Shi-Bin Yu</name>
<affiliation><nlm:aff id="aff2"><institution>School of Stomatology, Fourth Military Medical University</institution>
, Xi'an 710032,<country>China</country>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Dong, Guang Ying" sort="Dong, Guang Ying" uniqKey="Dong G" first="Guang-Ying" last="Dong">Guang-Ying Dong</name>
<affiliation><nlm:aff id="aff2"><institution>School of Stomatology, Fourth Military Medical University</institution>
, Xi'an 710032,<country>China</country>
</nlm:aff>
</affiliation>
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<series><title level="j">Acta Pharmacologica Sinica</title>
<idno type="ISSN">1671-4083</idno>
<idno type="eISSN">1745-7254</idno>
<imprint><date when="2011">2011</date>
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<front><div type="abstract" xml:lang="en"><sec><title>Aim:</title>
<p>To investigate the effect of genistein on bone homeostasis in mandibular subchondral bone of rats.</p>
</sec>
<sec><title>Methods:</title>
<p>Female SD rats were administered with genistein (10 and 50 mg/kg) or placebo by oral gavage for 6 weeks. Then the animals were sacrificed, and histomorphology and micro-structure of mandibular condyle were examined using HE staining and micro-CT analysis, respectively. The expression levels of alkaline phosphatase (ALP), osteocalcin (OC), osteoprotegerin (OPG), the receptor activator of nuclear factor κB ligand (RANKL) and estrogen receptors (ERs) in mandibular condyle were detected using real-time PCR. Cultured osteoblasts were prepared from rat mandibular condyle for in <italic>in vitro</italic>
study. The cells were treated with genistein (10<sup>−7</sup>
or 10<sup>−4</sup>
mol/L) for 48 h. The expression of the bone homeostasis-associated factors and estrogen receptors (ERs) was detected using real-time PCR, and ER silencing was performed.</p>
</sec>
<sec><title>Results:</title>
<p>At both the low- and high-doses, genistein significantly increased the bone mineral density (BMD) and bone volume, and resulted in thicker subchondral trabecular bone <italic>in vivo</italic>
. In both <italic>in vivo</italic>
and <italic>in vitro</italic>
study, the low-dose genistein significantly increased the expression of ALP, OC and OPG, but decreased the expression of RANKL and the RANKL/OPG ratio. The high-dose genistein decreased the expression of all these bone homeostasis-associated factors. Both the low and high doses of genistein significantly increased the expression of ERβ, while ERα expression was increased by the low dose genistein and decreased by the high dose genistein. ERβ silencing abrogated most of the effects of genistein treatment.</p>
</sec>
<sec><title>Conclusion:</title>
<p>In rat mandibular condylar subchondral bone, low-dose genistein increases bone formation and inhibit bone resorption, while excess genistein inhibits both bone formation and resorption. The effects of genistein were predominantly mediated through ERβ.</p>
</sec>
</div>
</front>
</TEI>
<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Acta Pharmacol Sin</journal-id>
<journal-id journal-id-type="iso-abbrev">Acta Pharmacol. Sin</journal-id>
<journal-title-group><journal-title>Acta Pharmacologica Sinica</journal-title>
</journal-title-group>
<issn pub-type="ppub">1671-4083</issn>
<issn pub-type="epub">1745-7254</issn>
<publisher><publisher-name>Nature Publishing Group</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">22120966</article-id>
<article-id pub-id-type="pmc">4010271</article-id>
<article-id pub-id-type="pii">aps2011136</article-id>
<article-id pub-id-type="doi">10.1038/aps.2011.136</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Original Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Dose-dependent effects of genistein on bone homeostasis in rats' mandibular subchondral bone</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Li</surname>
<given-names>Yong-qi</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
<xref ref-type="author-notes" rid="note1"><sup>#</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Xing</surname>
<given-names>Xiang-hui</given-names>
</name>
<xref ref-type="aff" rid="aff2">2</xref>
<xref ref-type="author-notes" rid="note1"><sup>#</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Wang</surname>
<given-names>Hui</given-names>
</name>
<xref ref-type="aff" rid="aff2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Weng</surname>
<given-names>Xi-li</given-names>
</name>
<xref ref-type="aff" rid="aff2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Yu</surname>
<given-names>Shi-bin</given-names>
</name>
<xref ref-type="aff" rid="aff2">2</xref>
<xref ref-type="corresp" rid="caf1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Dong</surname>
<given-names>Guang-ying</given-names>
</name>
<xref ref-type="aff" rid="aff2">2</xref>
<xref ref-type="corresp" rid="caf2">*</xref>
</contrib>
<aff id="aff1"><label>1</label>
<institution>Xijing Hospital, Fourth Military Medical University</institution>
, Xi'an 710032,<country>China</country>
</aff>
<aff id="aff2"><label>2</label>
<institution>School of Stomatology, Fourth Military Medical University</institution>
, Xi'an 710032,<country>China</country>
</aff>
</contrib-group>
<author-notes><corresp id="caf1"><label>*</label>
E-mail <email>yushibin@fmmu.edu.cn</email>
</corresp>
<corresp id="caf2"><label>*</label>
<email>donggy@fmmu.edu.cn</email>
</corresp>
<fn fn-type="present-address" id="note1"><label>#</label>
<p>These authors contributed equally to this work.</p>
</fn>
</author-notes>
<pub-date pub-type="ppub"><month>01</month>
<year>2012</year>
</pub-date>
<pub-date pub-type="epub"><day>28</day>
<month>11</month>
<year>2011</year>
</pub-date>
<volume>33</volume>
<issue>1</issue>
<fpage>66</fpage>
<lpage>74</lpage>
<history><date date-type="received"><day>23</day>
<month>07</month>
<year>2011</year>
</date>
<date date-type="accepted"><day>15</day>
<month>09</month>
<year>2011</year>
</date>
</history>
<permissions><copyright-statement>Copyright © 2012 CPS and SIMM</copyright-statement>
<copyright-year>2012</copyright-year>
<copyright-holder>CPS and SIMM</copyright-holder>
</permissions>
<abstract><sec><title>Aim:</title>
<p>To investigate the effect of genistein on bone homeostasis in mandibular subchondral bone of rats.</p>
</sec>
<sec><title>Methods:</title>
<p>Female SD rats were administered with genistein (10 and 50 mg/kg) or placebo by oral gavage for 6 weeks. Then the animals were sacrificed, and histomorphology and micro-structure of mandibular condyle were examined using HE staining and micro-CT analysis, respectively. The expression levels of alkaline phosphatase (ALP), osteocalcin (OC), osteoprotegerin (OPG), the receptor activator of nuclear factor κB ligand (RANKL) and estrogen receptors (ERs) in mandibular condyle were detected using real-time PCR. Cultured osteoblasts were prepared from rat mandibular condyle for in <italic>in vitro</italic>
study. The cells were treated with genistein (10<sup>−7</sup>
or 10<sup>−4</sup>
mol/L) for 48 h. The expression of the bone homeostasis-associated factors and estrogen receptors (ERs) was detected using real-time PCR, and ER silencing was performed.</p>
</sec>
<sec><title>Results:</title>
<p>At both the low- and high-doses, genistein significantly increased the bone mineral density (BMD) and bone volume, and resulted in thicker subchondral trabecular bone <italic>in vivo</italic>
. In both <italic>in vivo</italic>
and <italic>in vitro</italic>
study, the low-dose genistein significantly increased the expression of ALP, OC and OPG, but decreased the expression of RANKL and the RANKL/OPG ratio. The high-dose genistein decreased the expression of all these bone homeostasis-associated factors. Both the low and high doses of genistein significantly increased the expression of ERβ, while ERα expression was increased by the low dose genistein and decreased by the high dose genistein. ERβ silencing abrogated most of the effects of genistein treatment.</p>
</sec>
<sec><title>Conclusion:</title>
<p>In rat mandibular condylar subchondral bone, low-dose genistein increases bone formation and inhibit bone resorption, while excess genistein inhibits both bone formation and resorption. The effects of genistein were predominantly mediated through ERβ.</p>
</sec>
</abstract>
<kwd-group><kwd>genistein</kwd>
<kwd>estrogen receptor</kwd>
<kwd>mandibular subchondral bone</kwd>
<kwd>osteoblast</kwd>
<kwd>alkaline phosphatase</kwd>
<kwd>osteocalcin</kwd>
<kwd>osteoprotegerin</kwd>
<kwd>the receptor activator of nuclear factor κB ligand (RANKL)</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
</record>
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