雌激素抗骨质疏松的研究现状

雌激素抗骨质疏松的研究现状???(????????????,????610051)?????:R591.44;R977.12　　?????:C　　????:10020764(2002)04005502　　????????????????????,??????????。???????,????????????(??????????????????????)???????(??IL1、IL6、PTH、TNF、TGF、IGF?)?????????。?????????????????????????????,??????(osteoprotegrin,OPG)?????????(apoptosis)??。1　?????????1.1　???????????(OPGL)???　????????????????????????????,?????????????。1994?Amgen????????????cDNA??????????,?????????????????????、?????,???????????????????。??????,?????????????,???????OPG[1]。1997????Tsuda?[2]???????????????????????OPG???????,?????????????(osteoclastogenesisinhibitoryfactor,OCIF)。??????OPG?OCIF?????[3]。1998?,Lacey?Yasudan???????OPG?????,???OPGL,OPGL??OPG????????????[4,5]。1.2　OPG?OPGL???　OPG?OPGL??????????(osteoblast,OB)??[5,6],??????????(osteoclast,OC)??????????????????。????,OPGL??????OC???(??????????,CFUGM),?????????OC,???????OB????????[7]。??,??????OC????????OGL????????????(O?????)[]。??????OGL?????O?????????????????。?OG????OGL??,????O??????[4,5],????????????。???????????IL1、IL6、IL11、PTH、TNF?????OC??????,?????????OB?????????,??????????????OB?OPGL??,???OPG????????????OC?????????[9],????????????OC?????,??????OB??OPGL???????,?????OPG?OPGL????????????。1.3　????OPG???　????????OPG???,????????,?????OB???OPG??3?4?[10],?????????OPGL???。??,????????????IL1、IL6、IL11、PTH、TNF????????[11],????OB??OPGL。??,?????????OPG?????OPGL??,??OC?????,??????????????。2　??????2.1　???????　????(opoptosis)?????????(programmedcelldeath,PCD)????????????????,????????????,???????????????????,????????,?致????[12]。?????????????:??????,?????????,???????????,????,????????,????,???????????、???????????,???????????????????。???????????????????????,????????,?????????????????[13]。2.2　?????????　???????????????????????,?O????????,???????,??OB????????,??????,????耦?,????,????????。???????,????????55???????2002?4??25??4?PC8PCPPCC?,????,???????????,?致????????,????,?????,?????,????????。??,?????OC???,?????,????OB???????????????????。???????OB?????????[14],OC??????CFUGM??????????[15,16]。?????????????????????????OB?OC??。Hughes????,???????????????TGFβ??????????????,?????[16],Akatsu???OPG????OC??[17]。??,Vfeter?????????????????TNFα???OB??,???????????????????(IGF)???OB??[18]。????????????????????????????????。2.3　????????　????OB?OC??????????。Nirupama???????????7d?,OC????CFUGM??????,??????CFUGM????,?????????CFUGM?????[16]。?????????ICI164、384??????????,????????????CFUGM??????。?Hughes????????OC????????TGFB?????,???????TGFB????[16]。??,????????OB??TGFB[19],????IGF???,??TNFα??[11]?????OB??,??OC??,???????,??????,??????????????。????:[1]　WICKELGRENI.Miningthegenomefordrugs[J].Science,1999,285(5430):998.[2]　TSUDAE,GOTOM,MOCHIZUKIS,etal.Isolationofanovelcytokinefromhumanfibroblaststhatspecificallyinhibitsosteoclastogenesis[J].BiochemBiophysResCommun,1997,234(1):137.[3]　YASUDAH,SHIMAN,NAKAGAWAN,etal.Identityofosteoclastogenesisinhibitoryfactor(OCIF)andosteoprotegerin(OPG):amechanismbywhichOPGOCIFinhibitsosteoclastogenesisinvitro[J].Endocrinology,1998,139(3):1329.[4]　LACEYDL,TIMMSE,TANHL,etal.Osteoprotegerinligandisacytokinethatregulatesosteoclastdifferentiationandactivation[J].Cell,1998,93(2):165.[5]　YASUDAH,SHIMAN,NAKAGAWAN,etal.OsteoclastdifferentiationfactorisaligandforosteoprotegerinosteoclastogenesisinhibitoryfactorandisidenticaltoTRANCERANKL[J].ProcNatlAcadSciUSA,1998,95(7):3597.[6]　YAMAGUCHIK,KINOSAKIM,GOTOM,etal.Characterizationofstructuraldomainsofhumanosteoclastogenesisinhibitoryfactor[J].JBiolChem,1998,273(9):5117.[7]　JIMIE,AKIYAMAS,TSURUKAIT,etal.Osteoclastdifferentiationfactoractsasamultifunctionalregulatorinmurineosteoclastdifferentiationandfunction[J].JImmunol,1999,163(1):434.[8]　UDAGAWAN,TAKAHASHIN,JIMIE,etal.OsteoblastsstromalcellsstimulateosteoclastactivationthroughexpressionofosteoclastdifferentiationfactorRANKLbutnotmacrophagecolonystimulatingfactor:receptoractivatorofNFkappaBligand[J].Bone,1999,25(5):517.[9]　GREENFIELDEM,BIY,MIYAUCHIA.Regulationofosteoclastactivity[J].LifeSci,1999,65(11):1087.[10]　HOFBAUERLC,KHOSLAS,DUNSTANCR,etal.Estrogenstimulatesgeneexpressionandproteinproductionofosteoprogtegerininhumanosteoblasticcells[J].Endocrinology,1999,140(9):4367.[11]　ZHENGSX,VRINDTSY,LOPEZM,etal.Inereaseincytokineproduction(IL1beta,IL6TNFalphabutnotINFGamma,GMCSForLIF)bystimulatedwholebloodcellsinpostmenopausalosteoporosis[J].Maturitas,1997,26:63.[12]　STELLERH.Mechanismsandgenesofcellularsuicide[J].Science,1995,267:1445.[13]　LIYSHAROVVG,JIANGN.Ultrastructuralandlightmicroscopicevidenceofapoptosisaftermiddlecerebralarteryocclusionintherat[J].AmJPath,1995,146:1045.[14]　KAWAKAMIA,EGUCHIK,MATSUOKAN,etal.FasandFasligandinteractionisnecessaryforhumanosteoblastapoptosis[J].JBoneMinerRes,1997,12:1637.[15]　TAKASHIKAMEDA,HARAOLSHIKAIVA,TAKEKITSUTSUI.Detectionandcharacterizationofapoptosisinosteoclastsinvitro[J].BiochemBiophysResCommun,1995,207(2):753.[16]　HUGHESDE,DAIA,TIFFEEJC,etal.EstrogenpromotesapoptosisofmurineosteoclastsmediatedbyTGFbeta[J].NatMed,1996,2:1132.[17]　AKATSUT,MURAKAMIT,NISHIKAWAM,etal.Osteoclastogenesisinhibitoryfactorsuppressesosteoclastsurvivalbyinterferingintheinteractionofstromalcellswithosteoclast[J].BiochemBiophysResCommun,1998,250(2):229.[18]　HILLPA,TUMBERA,MEIKLEMC.Multipleextracellularsignalspromoteosteoblastsurvivalandapoptosis[J].Endocrinology,1997,138:3849.[19]　SUDAT,NAKAMURAI,JIMIE,etal.Regulationofosteoclastfunction[J].JBoneMinerRes,1997,6:869.????:20011224(????:???)?56?JournalofPostgraduatesofMedicine,April2002,Vol.25,No.4