γ抑制劑T0070907抑制破骨細(xì)胞生成及拮抗小鼠卵巢切除誘導(dǎo)骨量丟失

PAGE411引言骨穩(wěn)態(tài)環(huán)境的動(dòng)態(tài)平衡是破骨細(xì)胞的再吸收和成骨細(xì)胞的不斷生成共同維系的結(jié)果ADDINEN.CITE<EndNote><Cite><Author>IL</Author><Year>1997</Year><RecNum>257</RecNum><DisplayText><styleface="superscript">(4,5)</style></DisplayText><record><rec-number>257</rec-number><foreign-keys><keyapp="EN"db-id="rt2rea52gxd2vye0at8vfzzwttfrdwxx2dvt"timestamp="1542441972">257</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>WeissmanIL</author></authors></contributors><titles><title>EnforcedexpressionofBcl-2inmonocytesrescuesmacrophagesandpartiallyreversesosteopetrosisinop/opmice.%ALagasseE</title><secondary-title>Cell</secondary-title></titles><periodical><full-title>Cell</full-title></periodical><pages>1021-31</pages><volume>89</volume><number>7</number><dates><year>1997</year></dates><label>31.398</label><urls></urls></record></Cite><Cite><Author>H</Author><Year>1999</Year><RecNum>259</RecNum><record><rec-number>259</rec-number><foreign-keys><keyapp="EN"db-id="rt2rea52gxd2vye0at8vfzzwttfrdwxx2dvt"timestamp="1542442000">259</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>YoshidaH</author><author>SarosiI</author><author>TanHL</author><author>TimmsE</author><author>CapparelliC</author><author>MoronyS</author><author>Oliveira-dos-SantosAJ</author><author>VanG</author><author>ItieA</author><author>KhooW</author><author>WakehamA</author><author>DunstanCR</author><author>LaceyDL</author><author>MakTW</author><author>BoyleWJ</author><author>PenningerJM</author></authors></contributors><titles><title>OPGLisakeyregulatorofosteoclastogenesis,lymphocytedevelopmentandlymph-nodeorganogenesis.%AKongYY</title><secondary-title>Nature</secondary-title></titles><periodical><full-title>Nature</full-title></periodical><pages>315-23</pages><volume>397</volume><number>6717</number><dates><year>1999</year></dates><label>41.577</label><urls></urls></record></Cite></EndNote>(1,2)，過度的破骨細(xì)胞活動(dòng)會(huì)導(dǎo)致骨質(zhì)疏松等骨代謝疾病ADDINEN.CITE<EndNote><Cite><Author>IL</Author><Year>1997</Year><RecNum>257</RecNum><DisplayText><styleface="superscript">(4,5)</style></DisplayText><record><rec-number>257</rec-number><foreign-keys><keyapp="EN"db-id="rt2rea52gxd2vye0at8vfzzwttfrdwxx2dvt"timestamp="1542441972">257</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>WeissmanIL</author></authors></contributors><titles><title>EnforcedexpressionofBcl-2inmonocytesrescuesmacrophagesandpartiallyreversesosteopetrosisinop/opmice.%ALagasseE</title><secondary-title>Cell</secondary-title></titles><periodical><full-title>Cell</full-title></periodical><pages>1021-31</pages><volume>89</volume><number>7</number><dates><year>1997</year></dates><label>31.398</label><urls></urls></record></Cite><Cite><Author>H</Author><Year>1999</Year><RecNum>259</RecNum><record><rec-number>259</rec-number><foreign-keys><keyapp="EN"db-id="rt2rea52gxd2vye0at8vfzzwttfrdwxx2dvt"timestamp="1542442000">259</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>YoshidaH</author><author>SarosiI</author><author>TanHL</author><author>TimmsE</author><author>CapparelliC</author><author>MoronyS</author><author>Oliveira-dos-SantosAJ</author><author>VanG</author><author>ItieA</author><author>KhooW</author><author>WakehamA</author><author>DunstanCR</author><author>LaceyDL</author><author>MakTW</author><author>BoyleWJ</author><author>PenningerJM</author></authors></contributors><titles><title>OPGLisakeyregulatorofosteoclastogenesis,lymphocytedevelopmentandlymph-nodeorganogenesis.%AKongYY</title><secondary-title>Nature</secondary-title></titles><periodical><full-title>Nature</full-title></periodical><pages>315-23</pages><volume>397</volume><number>6717</number><dates><year>1999</year></dates><label>41.577</label><urls></urls></record></Cite></EndNote>(2)。骨質(zhì)疏松癥被認(rèn)為是一種以骨量減少、骨組織構(gòu)造異樣、骨脆性及骨折增多為特性的慢性病癥，現(xiàn)已變成世界性的公共衛(wèi)生難題ADDINEN.CITE<EndNote><Cite><Author>IL</Author><Year>1997</Year><RecNum>257</RecNum><DisplayText><styleface="superscript">(4,5)</style></DisplayText><record><rec-number>257</rec-number><foreign-keys><keyapp="EN"db-id="rt2rea52gxd2vye0at8vfzzwttfrdwxx2dvt"timestamp="1542441972">257</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>WeissmanIL</author></authors></contributors><titles><title>EnforcedexpressionofBcl-2inmonocytesrescuesmacrophagesandpartiallyreversesosteopetrosisinop/opmice.%ALagasseE</title><secondary-title>Cell</secondary-title></titles><periodical><full-title>Cell</full-title></periodical><pages>1021-31</pages><volume>89</volume><number>7</number><dates><year>1997</year></dates><label>31.398</label><urls></urls></record></Cite><Cite><Author>H</Author><Year>1999</Year><RecNum>259</RecNum><record><rec-number>259</rec-number><foreign-keys><keyapp="EN"db-id="rt2rea52gxd2vye0at8vfzzwttfrdwxx2dvt"timestamp="1542442000">259</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>YoshidaH</author><author>SarosiI</author><author>TanHL</author><author>TimmsE</author><author>CapparelliC</author><author>MoronyS</author><author>Oliveira-dos-SantosAJ</author><author>VanG</author><author>ItieA</author><author>KhooW</author><author>WakehamA</author><author>DunstanCR</author><author>LaceyDL</author><author>MakTW</author><author>BoyleWJ</author><author>PenningerJM</author></authors></contributors><titles><title>OPGLisakeyregulatorofosteoclastogenesis,lymphocytedevelopmentandlymph-nodeorganogenesis.%AKongYY</title><secondary-title>Nature</secondary-title></titles><periodical><full-title>Nature</full-title></periodical><pages>315-23</pages><volume>397</volume><number>6717</number><dates><year>1999</year></dates><label>41.577</label><urls></urls></record></Cite></EndNote>(3)。當(dāng)前世界有10.2億左右的人口罹患上骨質(zhì)疏松病癥，預(yù)計(jì)到2030年，人數(shù)將增加至13.6億ADDINEN.CITE<EndNote><Cite><Author>IL</Author><Year>1997</Year><RecNum>257</RecNum><DisplayText><styleface="superscript">(4,5)</style></DisplayText><record><rec-number>257</rec-number><foreign-keys><keyapp="EN"db-id="rt2rea52gxd2vye0at8vfzzwttfrdwxx2dvt"timestamp="1542441972">257</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>WeissmanIL</author></authors></contributors><titles><title>EnforcedexpressionofBcl-2inmonocytesrescuesmacrophagesandpartiallyreversesosteopetrosisinop/opmice.%ALagasseE</title><secondary-title>Cell</secondary-title></titles><periodical><full-title>Cell</full-title></periodical><pages>1021-31</pages><volume>89</volume><number>7</number><dates><year>1997</year></dates><label>31.398</label><urls></urls></record></Cite><Cite><Author>H</Author><Year>1999</Year><RecNum>259</RecNum><record><rec-number>259</rec-number><foreign-keys><keyapp="EN"db-id="rt2rea52gxd2vye0at8vfzzwttfrdwxx2dvt"timestamp="1542442000">259</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>YoshidaH</author><author>SarosiI</author><author>TanHL</author><author>TimmsE</author><author>CapparelliC</author><author>MoronyS</author><author>Oliveira-dos-SantosAJ</author><author>VanG</author><author>ItieA</author><author>KhooW</author><author>WakehamA</author><author>DunstanCR</author><author>LaceyDL</author><author>MakTW</author><author>BoyleWJ</author><author>PenningerJM</author></authors></contributors><titles><title>OPGLisakeyregulatorofosteoclastogenesis,lymphocytedevelopmentandlymph-nodeorganogenesis.%AKongYY</title><secondary-title>Nature</secondary-title></titles><periodical><full-title>Nature</full-title></periodical><pages>315-23</pages><volume>397</volume><number>6717</number><dates><year>1999</year></dates><label>41.577</label><urls></urls></record></Cite></EndNote>(4)。OPG/NF-κB激活RANK/RANKL復(fù)合物應(yīng)是一個(gè)在骨新陳代謝中起極其重要調(diào)節(jié)作用的子系統(tǒng)，調(diào)控成骨細(xì)胞介導(dǎo)的骨基質(zhì)制備以及破骨細(xì)胞介導(dǎo)的骨吸收進(jìn)展的動(dòng)態(tài)平衡ADDINEN.CITE<EndNote><Cite><Author>IL</Author><Year>1997</Year><RecNum>257</RecNum><DisplayText><styleface="superscript">(4,5)</style></DisplayText><record><rec-number>257</rec-number><foreign-keys><keyapp="EN"db-id="rt2rea52gxd2vye0at8vfzzwttfrdwxx2dvt"timestamp="1542441972">257</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>WeissmanIL</author></authors></contributors><titles><title>EnforcedexpressionofBcl-2inmonocytesrescuesmacrophagesandpartiallyreversesosteopetrosisinop/opmice.%ALagasseE</title><secondary-title>Cell</secondary-title></titles><periodical><full-title>Cell</full-title></periodical><pages>1021-31</pages><volume>89</volume><number>7</number><dates><year>1997</year></dates><label>31.398</label><urls></urls></record></Cite><Cite><Author>H</Author><Year>1999</Year><RecNum>259</RecNum><record><rec-number>259</rec-number><foreign-keys><keyapp="EN"db-id="rt2rea52gxd2vye0at8vfzzwttfrdwxx2dvt"timestamp="1542442000">259</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>YoshidaH</author><author>SarosiI</author><author>TanHL</author><author>TimmsE</author><author>CapparelliC</author><author>MoronyS</author><author>Oliveira-dos-SantosAJ</author><author>VanG</author><author>ItieA</author><author>KhooW</author><author>WakehamA</author><author>DunstanCR</author><author>LaceyDL</author><author>MakTW</author><author>BoyleWJ</author><author>PenningerJM</author></authors></contributors><titles><title>OPGLisakeyregulatorofosteoclastogenesis,lymphocytedevelopmentandlymph-nodeorganogenesis.%AKongYY</title><secondary-title>Nature</secondary-title></titles><periodical><full-title>Nature</full-title></periodical><pages>315-23</pages><volume>397</volume><number>6717</number><dates><year>1999</year></dates><label>41.577</label><urls></urls></record></Cite></EndNote>(5)。

RANKL是一種與骨代謝有著密切聯(lián)系的細(xì)胞因子，積極參加到破骨細(xì)胞的動(dòng)態(tài)形成過程中，推動(dòng)破骨細(xì)胞的成熟與分化ADDINEN.CITE<EndNote><Cite><Author>IL</Author><Year>1997</Year><RecNum>257</RecNum><DisplayText><styleface="superscript">(4,5)</style></DisplayText><record><rec-number>257</rec-number><foreign-keys><keyapp="EN"db-id="rt2rea52gxd2vye0at8vfzzwttfrdwxx2dvt"timestamp="1542441972">257</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>WeissmanIL</author></authors></contributors><titles><title>EnforcedexpressionofBcl-2inmonocytesrescuesmacrophagesandpartiallyreversesosteopetrosisinop/opmice.%ALagasseE</title><secondary-title>Cell</secondary-title></titles><periodical><full-title>Cell</full-title></periodical><pages>1021-31</pages><volume>89</volume><number>7</number><dates><year>1997</year></dates><label>31.398</label><urls></urls></record></Cite><Cite><Author>H</Author><Year>1999</Year><RecNum>259</RecNum><record><rec-number>259</rec-number><foreign-keys><keyapp="EN"db-id="rt2rea52gxd2vye0at8vfzzwttfrdwxx2dvt"timestamp="1542442000">259</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>YoshidaH</author><author>SarosiI</author><author>TanHL</author><author>TimmsE</author><author>CapparelliC</author><author>MoronyS</author><author>Oliveira-dos-SantosAJ</author><author>VanG</author><author>ItieA</author><author>KhooW</author><author>WakehamA</author><author>DunstanCR</author><author>LaceyDL</author><author>MakTW</author><author>BoyleWJ</author><author>PenningerJM</author></authors></contributors><titles><title>OPGLisakeyregulatorofosteoclastogenesis,lymphocytedevelopmentandlymph-nodeorganogenesis.%AKongYY</title><secondary-title>Nature</secondary-title></titles><periodical><full-title>Nature</full-title></periodical><pages>315-23</pages><volume>397</volume><number>6717</number><dates><year>1999</year></dates><label>41.577</label><urls></urls></record></Cite></EndNote>(6)。RANKL-RANKL復(fù)合物（RANKL受體）可以引發(fā)調(diào)節(jié)因子（如TRAF6基因）的秩監(jiān)測(cè)分離及其隨后的MAPK激活A(yù)DDINEN.CITE<EndNote><Cite><Author>IL</Author><Year>1997</Year><RecNum>257</RecNum><DisplayText><styleface="superscript">(4,5)</style></DisplayText><record><rec-number>257</rec-number><foreign-keys><keyapp="EN"db-id="rt2rea52gxd2vye0at8vfzzwttfrdwxx2dvt"timestamp="1542441972">257</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>WeissmanIL</author></authors></contributors><titles><title>EnforcedexpressionofBcl-2inmonocytesrescuesmacrophagesandpartiallyreversesosteopetrosisinop/opmice.%ALagasseE</title><secondary-title>Cell</secondary-title></titles><periodical><full-title>Cell</full-title></periodical><pages>1021-31</pages><volume>89</volume><number>7</number><dates><year>1997</year></dates><label>31.398</label><urls></urls></record></Cite><Cite><Author>H</Author><Year>1999</Year><RecNum>259</RecNum><record><rec-number>259</rec-number><foreign-keys><keyapp="EN"db-id="rt2rea52gxd2vye0at8vfzzwttfrdwxx2dvt"timestamp="1542442000">259</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>YoshidaH</author><author>SarosiI</author><author>TanHL</author><author>TimmsE</author><author>CapparelliC</author><author>MoronyS</author><author>Oliveira-dos-SantosAJ</author><author>VanG</author><author>ItieA</author><author>KhooW</author><author>WakehamA</author><author>DunstanCR</author><author>LaceyDL</author><author>MakTW</author><author>BoyleWJ</author><author>PenningerJM</author></authors></contributors><titles><title>OPGLisakeyregulatorofosteoclastogenesis,lymphocytedevelopmentandlymph-nodeorganogenesis.%AKongYY</title><secondary-title>Nature</secondary-title></titles><periodical><full-title>Nature</full-title></periodical><pages>315-23</pages><volume>397</volume><number>6717</number><dates><year>1999</year></dates><label>41.577</label><urls></urls></record></Cite></EndNote>(7,8)，從而上調(diào)NFATc1和c-Fos的表達(dá)水平，誘導(dǎo)破骨細(xì)胞的發(fā)生ADDINEN.CITE<EndNote><Cite><Author>IL</Author><Year>1997</Year><RecNum>257</RecNum><DisplayText><styleface="superscript">(4,5)</style></DisplayText><record><rec-number>257</rec-number><foreign-keys><keyapp="EN"db-id="rt2rea52gxd2vye0at8vfzzwttfrdwxx2dvt"timestamp="1542441972">257</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>WeissmanIL</author></authors></contributors><titles><title>EnforcedexpressionofBcl-2inmonocytesrescuesmacrophagesandpartiallyreversesosteopetrosisinop/opmice.%ALagasseE</title><secondary-title>Cell</secondary-title></titles><periodical><full-title>Cell</full-title></periodical><pages>1021-31</pages><volume>89</volume><number>7</number><dates><year>1997</year></dates><label>31.398</label><urls></urls></record></Cite><Cite><Author>H</Author><Year>1999</Year><RecNum>259</RecNum><record><rec-number>259</rec-number><foreign-keys><keyapp="EN"db-id="rt2rea52gxd2vye0at8vfzzwttfrdwxx2dvt"timestamp="1542442000">259</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>YoshidaH</author><author>SarosiI</author><author>TanHL</author><author>TimmsE</author><author>CapparelliC</author><author>MoronyS</author><author>Oliveira-dos-SantosAJ</author><author>VanG</author><author>ItieA</author><author>KhooW</author><author>WakehamA</author><author>DunstanCR</author><author>LaceyDL</author><author>MakTW</author><author>BoyleWJ</author><author>PenningerJM</author></authors></contributors><titles><title>OPGLisakeyregulatorofosteoclastogenesis,lymphocytedevelopmentandlymph-nodeorganogenesis.%AKongYY</title><secondary-title>Nature</secondary-title></titles><periodical><full-title>Nature</full-title></periodical><pages>315-23</pages><volume>397</volume><number>6717</number><dates><year>1999</year></dates><label>41.577</label><urls></urls></record></Cite></EndNote>(9)。OPG應(yīng)是由成骨細(xì)胞分泌的可溶性蛋白質(zhì)，借助和RANKL競(jìng)爭(zhēng)結(jié)合的手段而進(jìn)一步提高骨密度，達(dá)到抑制骨吸取的最終目標(biāo)ADDINEN.CITE<EndNote><Cite><Author>IL</Author><Year>1997</Year><RecNum>257</RecNum><DisplayText><styleface="superscript">(4,5)</style></DisplayText><record><rec-number>257</rec-number><foreign-keys><keyapp="EN"db-id="rt2rea52gxd2vye0at8vfzzwttfrdwxx2dvt"timestamp="1542441972">257</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>WeissmanIL</author></authors></contributors><titles><title>EnforcedexpressionofBcl-2inmonocytesrescuesmacrophagesandpartiallyreversesosteopetrosisinop/opmice.%ALagasseE</title><secondary-title>Cell</secondary-title></titles><periodical><full-title>Cell</full-title></periodical><pages>1021-31</pages><volume>89</volume><number>7</number><dates><year>1997</year></dates><label>31.398</label><urls></urls></record></Cite><Cite><Author>H</Author><Year>1999</Year><RecNum>259</RecNum><record><rec-number>259</rec-number><foreign-keys><keyapp="EN"db-id="rt2rea52gxd2vye0at8vfzzwttfrdwxx2dvt"timestamp="1542442000">259</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>YoshidaH</author><author>SarosiI</author><author>TanHL</author><author>TimmsE</author><author>CapparelliC</author><author>MoronyS</author><author>Oliveira-dos-SantosAJ</author><author>VanG</author><author>ItieA</author><author>KhooW</author><author>WakehamA</author><author>DunstanCR</author><author>LaceyDL</author><author>MakTW</author><author>BoyleWJ</author><author>PenningerJM</author></authors></contributors><titles><title>OPGLisakeyregulatorofosteoclastogenesis,lymphocytedevelopmentandlymph-nodeorganogenesis.%AKongYY</title><secondary-title>Nature</secondary-title></titles><periodical><full-title>Nature</full-title></periodical><pages>315-23</pages><volume>397</volume><number>6717</number><dates><year>1999</year></dates><label>41.577</label><urls></urls></record></Cite></EndNote>(10)。RANKL/OPG的值能視為骨量與骨質(zhì)安全的極其重要指標(biāo)ADDINEN.CITE<EndNote><Cite><Author>IL</Author><Year>1997</Year><RecNum>257</RecNum><DisplayText><styleface="superscript">(4,5)</style></DisplayText><record><rec-number>257</rec-number><foreign-keys><keyapp="EN"db-id="rt2rea52gxd2vye0at8vfzzwttfrdwxx2dvt"timestamp="1542441972">257</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>WeissmanIL</author></authors></contributors><titles><title>EnforcedexpressionofBcl-2inmonocytesrescuesmacrophagesandpartiallyreversesosteopetrosisinop/opmice.%ALagasseE</title><secondary-title>Cell</secondary-title></titles><periodical><full-title>Cell</full-title></periodical><pages>1021-31</pages><volume>89</volume><number>7</number><dates><year>1997</year></dates><label>31.398</label><urls></urls></record></Cite><Cite><Author>H</Author><Year>1999</Year><RecNum>259</RecNum><record><rec-number>259</rec-number><foreign-keys><keyapp="EN"db-id="rt2rea52gxd2vye0at8vfzzwttfrdwxx2dvt"timestamp="1542442000">259</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>YoshidaH</author><author>SarosiI</author><author>TanHL</author><author>TimmsE</author><author>CapparelliC</author><author>MoronyS</author><author>Oliveira-dos-SantosAJ</author><author>VanG</author><author>ItieA</author><author>KhooW</author><author>WakehamA</author><author>DunstanCR</author><author>LaceyDL</author><author>MakTW</author><author>BoyleWJ</author><author>PenningerJM</author></authors></contributors><titles><title>OPGLisakeyregulatorofosteoclastogenesis,lymphocytedevelopmentandlymph-nodeorganogenesis.%AKongYY</title><secondary-title>Nature</secondary-title></titles><periodical><full-title>Nature</full-title></periodical><pages>315-23</pages><volume>397</volume><number>6717</number><dates><year>1999</year></dates><label>41.577</label><urls></urls></record></Cite></EndNote>(11)。因而，由RANKL管理控制的信號(hào)源通路可以成為骨細(xì)胞的生物降解等病癥的藥理靶點(diǎn)ADDINEN.CITE<EndNote><Cite><Author>IL</Author><Year>1997</Year><RecNum>257</RecNum><DisplayText><styleface="superscript">(4,5)</style></DisplayText><record><rec-number>257</rec-number><foreign-keys><keyapp="EN"db-id="rt2rea52gxd2vye0at8vfzzwttfrdwxx2dvt"timestamp="1542441972">257</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>WeissmanIL</author></authors></contributors><titles><title>EnforcedexpressionofBcl-2inmonocytesrescuesmacrophagesandpartiallyreversesosteopetrosisinop/opmice.%ALagasseE</title><secondary-title>Cell</secondary-title></titles><periodical><full-title>Cell</full-title></periodical><pages>1021-31</pages><volume>89</volume><number>7</number><dates><year>1997</year></dates><label>31.398</label><urls></urls></record></Cite><Cite><Author>H</Author><Year>1999</Year><RecNum>259</RecNum><record><rec-number>259</rec-number><foreign-keys><keyapp="EN"db-id="rt2rea52gxd2vye0at8vfzzwttfrdwxx2dvt"timestamp="1542442000">259</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>YoshidaH</author><author>SarosiI</author><author>TanHL</author><author>TimmsE</author><author>CapparelliC</author><author>MoronyS</author><author>Oliveira-dos-SantosAJ</author><author>VanG</author><author>ItieA</author><author>KhooW</author><author>WakehamA</author><author>DunstanCR</author><author>LaceyDL</author><author>MakTW</author><author>BoyleWJ</author><author>PenningerJM</author></authors></contributors><titles><title>OPGLisakeyregulatorofosteoclastogenesis,lymphocytedevelopmentandlymph-nodeorganogenesis.%AKongYY</title><secondary-title>Nature</secondary-title></titles><periodical><full-title>Nature</full-title></periodical><pages>315-23</pages><volume>397</volume><number>6717</number><dates><year>1999</year></dates><label>41.577</label><urls></urls></record></Cite></EndNote>(12)?？惯^氧化物酶體增殖物激活受體γ（PPAR-γ）的藥物因其阻礙多種癌細(xì)胞生長(zhǎng)的巨大潛力而成為眾多課題研究的對(duì)象。PPAR-γ不僅介入到成骨細(xì)胞的生成過程中ADDINEN.CITE<EndNote><Cite><Author>IL</Author><Year>1997</Year><RecNum>257</RecNum><DisplayText><styleface="superscript">(4,5)</style></DisplayText><record><rec-number>257</rec-number><foreign-keys><keyapp="EN"db-id="rt2rea52gxd2vye0at8vfzzwttfrdwxx2dvt"timestamp="1542441972">257</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>WeissmanIL</author></authors></contributors><titles><title>EnforcedexpressionofBcl-2inmonocytesrescuesmacrophagesandpartiallyreversesosteopetrosisinop/opmice.%ALagasseE</title><secondary-title>Cell</secondary-title></titles><periodical><full-title>Cell</full-title></periodical><pages>1021-31</pages><volume>89</volume><number>7</number><dates><year>1997</year></dates><label>31.398</label><urls></urls></record></Cite><Cite><Author>H</Author><Year>1999</Year><RecNum>259</RecNum><record><rec-number>259</rec-number><foreign-keys><keyapp="EN"db-id="rt2rea52gxd2vye0at8vfzzwttfrdwxx2dvt"timestamp="1542442000">259</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>YoshidaH</author><author>SarosiI</author><author>TanHL</author><author>TimmsE</author><author>CapparelliC</author><author>MoronyS</author><author>Oliveira-dos-SantosAJ</author><author>VanG</author><author>ItieA</author><author>KhooW</author><author>WakehamA</author><author>DunstanCR</author><author>LaceyDL</author><author>MakTW</author><author>BoyleWJ</author><author>PenningerJM</author></authors></contributors><titles><title>OPGLisakeyregulatorofosteoclastogenesis,lymphocytedevelopmentandlymph-nodeorganogenesis.%AKongYY</title><secondary-title>Nature</secondary-title></titles><periodical><full-title>Nature</full-title></periodical><pages>315-23</pages><volume>397</volume><number>6717</number><dates><year>1999</year></dates><label>41.577</label><urls></urls></record></Cite></EndNote>(13)，同時(shí)其在破骨細(xì)胞中的表達(dá)水平也可以被徹底上調(diào)ADDINEN.CITE<EndNote><Cite><Author>IL</Author><Year>1997</Year><RecNum>257</RecNum><DisplayText><styleface="superscript">(4,5)</style></DisplayText><record><rec-number>257</rec-number><foreign-keys><keyapp="EN"db-id="rt2rea52gxd2vye0at8vfzzwttfrdwxx2dvt"timestamp="1542441972">257</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>WeissmanIL</author></authors></contributors><titles><title>EnforcedexpressionofBcl-2inmonocytesrescuesmacrophagesandpartiallyreversesosteopetrosisinop/opmice.%ALagasseE</title><secondary-title>Cell</secondary-title></titles><periodical><full-title>Cell</full-title></periodical><pages>1021-31</pages><volume>89</volume><number>7</number><dates><year>1997</year></dates><label>31.398</label><urls></urls></record></Cite><Cite><Author>H</Author><Year>1999</Year><RecNum>259</RecNum><record><rec-number>259</rec-number><foreign-keys><keyapp="EN"db-id="rt2rea52gxd2vye0at8vfzzwttfrdwxx2dvt"timestamp="1542442000">259</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>YoshidaH</author><author>SarosiI</author><author>TanHL</author><author>TimmsE</author><author>CapparelliC</author><author>MoronyS</author><author>Oliveira-dos-SantosAJ</author><author>VanG</author><author>ItieA</author><author>KhooW</author><author>WakehamA</author><author>DunstanCR</author><author>LaceyDL</author><author>MakTW</author><author>BoyleWJ</author><author>PenningerJM</author></authors></contributors><titles><title>OPGLisakeyregulatorofosteoclastogenesis,lymphocytedevelopmentandlymph-nodeorganogenesis.%AKongYY</title><secondary-title>Nature</secondary-title></titles><periodical><full-title>Nature</full-title></periodical><pages>315-23</pages><volume>397</volume><number>6717</number><dates><year>1999</year></dates><label>41.577</label><urls></urls></record></Cite></EndNote>(14,15)。PPAR-γ被公認(rèn)為外源性藥物的藥理靶點(diǎn)ADDINEN.CITE<EndNote><Cite><Author>IL</Author><Year>1997</Year><RecNum>257</RecNum><DisplayText><styleface="superscript">(4,5)</style></DisplayText><record><rec-number>257</rec-number><foreign-keys><keyapp="EN"db-id="rt2rea52gxd2vye0at8vfzzwttfrdwxx2dvt"timestamp="1542441972">257</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>WeissmanIL</author></authors></contributors><titles><title>EnforcedexpressionofBcl-2inmonocytesrescuesmacrophagesandpartiallyreversesosteopetrosisinop/opmice.%ALagasseE</title><secondary-title>Cell</secondary-title></titles><periodical><full-title>Cell</full-title></periodical><pages>1021-31</pages><volume>89</volume><number>7</number><dates><year>1997</year></dates><label>31.398</label><urls></urls></record></Cite><Cite><Author>H</Author><Year>1999</Year><RecNum>259</RecNum><record><rec-number>259</rec-number><foreign-keys><keyapp="EN"db-id="rt2rea52gxd2vye0at8vfzzwttfrdwxx2dvt"timestamp="1542442000">259</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributor