Serum amyloid A inhibits osteoclast differentiation to maintain macrophage function

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: IFN regulatory factor 8;    c‐;    Fos;    NFATc1;    TLR;   

DOI  :  10.1189/jlb.3A0415-173R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

SerumamyloidAisanacutephaseproteinthatiselevatedunderinflammatoryconditions.Additionally,theserumlevelsofserumamyloidAareassociatedwiththeprogressionofinflammatoryarthritis;thus,serumamyloidAmightbeinvolvedintheregulationofosteoclastdifferentiation.Inthepresentstudy,weexaminedtheeffectsofserumamyloidAonosteoclastdifferentiationandfunction.Whenbonemarrow‐derivedmacrophages,asosteoclastprecursors,werestimulatedwithserumamyloidAinthepresenceofM‐CSFandreceptoractivatorofnuclearfactor‐κBligand,osteoclastdifferentiationanditsbone‐resorptionactivityweresubstantiallyinhibited.TLR2wasimportantintheinhibitoryeffectofserumamyloidAonosteoclastdifferentiation,becauseserumamyloidAstimulatedTLR2.Theinhibitoryeffectwasabsentinbonemarrow‐derivedmacrophagesobtainedfromTLR2‐deficientmice.Furthermore,serumamyloidAinhibitedtheexpressionofc‐FosandnuclearfactorofactivatedTcellsc1,whicharecrucialtranscriptionfactorsforosteoclastdifferentiation,butpreventeddownregulationofIFNregulatoryfactor‐8,anegativeregulatorofosteoclastdifferentiation.Incontrast,serumamyloidAsustainedtheendocyticcapacityofbonemarrow‐derivedmacrophagesandtheirabilitytoinducetheproinflammatorycytokines,IL‐6,IL‐1β,andTNF‐α.Takentogether,theseresultssuggestthatserumamyloidA,whenincreasedbyinflammatoryconditions,inhibitsdifferentiationofmacrophagestoosteoclasts,likelytomaintainmacrophagefunctionforhostdefense...

【 授权许可】

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