γ抑制剂T0070907抑制破骨细胞生成及拮抗小鼠卵巢切除诱导骨量丢失

PAGE411引言骨稳态环境的动态平衡是破骨细胞的再吸收和成骨细胞的不断生成共同维系的结果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)，过度的破骨细胞活动会导致骨质疏松等骨代谢疾病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)。骨质疏松症被认为是一种以骨量减少、骨组织构造异样、骨脆性及骨折增多为特性的慢性病症，现已变成世界性的公共卫生难题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)。当前世界有10.2亿左右的人口罹患上骨质疏松病症，预计到2030年，人数将增加至13.6亿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复合物应是一个在骨新陈代谢中起极其重要调节作用的子系统，调控成骨细胞介导的骨基质制备以及破骨细胞介导的骨吸收进展的动态平衡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是一种与骨代谢有着密切联系的细胞因子，积极参加到破骨细胞的动态形成过程中，推动破骨细胞的成熟与分化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复合物（RANKL受体）可以引发调节因子（如TRAF6基因）的秩监测分离及其随后的MAPK激活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>(7,8)，从而上调NFATc1和c-Fos的表达水平，诱导破骨细胞的发生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应是由成骨细胞分泌的可溶性蛋白质，借助和RANKL竞争结合的手段而进一步提高骨密度，达到抑制骨吸取的最终目标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的值能视为骨量与骨质安全的极其重要指标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管理控制的信号源通路可以成为骨细胞的生物降解等病症的药理靶点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)。抗过氧化物酶体增殖物激活受体γ（PPAR-γ）的药物因其阻碍多种癌细胞生长的巨大潜力而成为众多课题研究的对象。PPAR-γ不仅介入到成骨细胞的生成过程中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)，同时其在破骨细胞中的表达水平也可以被彻底上调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被公认为外源性药物的药理靶点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