作者：LiuS,etal
翻译：麻贞贞（北医三院风湿科）
目的：骨血管生成与成骨密切相关，提示促血管生成分子与成骨细胞之间存在关联。血管生成前分子血管内皮生长因子（VEGF）及其受体Flt-1、Flk-1和成纤维细胞生长因子（FGF-2）在类风湿性关节炎（RA）发病机制中起着重要作用。白细胞介素（IL-35）在RA中被证明是一种抗炎细胞因子。然而，所涉及的机制还没有完全理解。本研究旨在探讨白介素-35是否对RA成骨细胞的血管生成及其相关的信号通路有影响。
方法：用成骨细胞株MC3T3E1细胞体外研究白介素-35对成骨细胞增殖、凋亡及促血管生成分子mRNA和蛋白的影响。采用细胞增殖试剂盒-8（CCK-8）法和流式细胞术检测白介素-35对细胞增殖和凋亡的影响。分别采用实时聚合酶链反应（PCR）和酶联免疫吸附试验（ELISA）检测促血管生成分子的表达及白介素-35、骨形成、血管生成之间的关系及相关的信号通路。
结果：白细胞介素-35在体外呈剂量依赖性促进成骨细胞增殖，并抑制其凋亡。白介素-35增加了成骨细胞对基底和肿瘤坏死因子α诱导的促血管生成分子的表达。白花丹素阻断Th17/IL-17信号通路可抑制IL-35在成骨细胞中的促血管生成作用。
结论：这些结果表明，IL-35通过促进成骨细胞增殖、抑制凋亡和通过Th17/IL-17相关信号通路上调促血管生成分子来促进骨形成和血管生成。我们的发现扩展了目前对RA骨形成和血管生成调控机制的理解。
附原文：
OBJECTIVES:Angiogenesisinboneandosteogenesisappeartobecloselylinked,suggestingtheexistenceofmolecularcrosstalkbetweenpro-angiogenicmoleculesandosteoblasts.Thepro-angiogenicmoleculesvascularendothelialgrowthfactor(VEGF)withitsreceptorsFlt-1,Flk-1andfibroblastgrowthfactor(FGF)-2playacrucialroleinbornformation,anearlyandcriticaleventinthepathogenesisofrheumatoidarthritis(RA).Interleukin(IL)-35isdemonstratedtobeananti-inflammatorycytokineinRA.However,themechanismsinvolvedarenotfullyunderstood.ThisstudyaimstoinvestigatewhetherIL-35hasanimpactonangiogenesisinosteoblastsanditsrelatedsignallingpathwayinRA.
METHODS:TheeffectsofIL-35onosteoblastsproliferation,apoptosisandpro-angiogenicmoleculesmRNAandproteinwereexaminedusingosteoblast-likeMC3T3E1cellsinvitro.TheeffectsofIL-35onproliferationandapoptosiswereexaminedusingcellcountingkit-8(CCK-8)assayandflowcytometry,respectively.Pro-angiogenicmoleculesexpressionwereassessedbyrealtimePCRandELISA,respectively.ThesignallingpathwaybetweenIL-35,boneformation,angiogenesisandsignallingpathwaywasalsoinvestigated.
RESULTS:IL-35promotedosteoblastsproliferationandinhibitedapoptosisinadose-dependentmannerinvitro.IL-35increasedbasalandTNF-alphainducedpro-angiogenicmoleculesexpressionbyosteoblasts.BlockingtheTh17/IL-17signallingpathwaywithplumbagininhibitedthepro-angiogeniceffectsofIL-35inosteoblasts.
CONCLUSIONS:TheseresultssuggestedthatIL-35promotesboneformationandangiogenesisbyfosteringosteoblastsproliferation,inhibitingapoptosisandupregulatingpro-angiogenicmoleculesthroughTh17/IL-17related-signallingpathway.OurfindingsextendthecurrentunderstandingofmechanismsmodulatingboneformationandangiogenesisinRA.
引自：LiuS,LiY,XiaL,ShenH,LuJ.IL-35preventbonelossthroughpromotionofboneformationandangiogenesisinrheumatoidarthritis.Clinicalandexperimentalrheumatology
治疗白癜风的偏方北京治疗白癜风需花多少钱