NewToolsforIdentifyingInflammatoryandOsteoarthritisPhenotypesVirginiaByersKraus,MD,PhDProfessorofMedicine医学教授DukeUniversitySchoolofMedicine杜克大学医学院DukeInstituteforMolecularPhysiology杜克分子生理研究所Durham,NCSeptember2013识别炎症与骨关节炎表型的新工具HistoryofOsteoarthritisFromthetimesofHippocratesallformsofchronicarthritiswereregardedasmanifestationsofgout.(DequekerandLuyten,2008;AnnRheumDis,67:5-10).SirArchibaldGarrodcoinedtheterm‘osteoarthritis’(OA)in1890.Debatehasragedeversince–isOAamechanical(‘non-inflammatory’)oraninflammatorydisease?1890年，ArchibaldGarrod爵士提出了”骨关节(Osteoarthritis)”(OA)这个名词.争论一直持续至今–OA究竟是一种机械性(‘非炎症’)或是一种炎症性疾病？骨关节炎的历史从希波克拉底时期，所有形式的慢性关节炎都被认为是痛风的表现HistoryofOsteoarthritis骨关节炎的历史OsteoarthritisisBOTHamechanicalandaninflammatorydisease.骨关节炎既是一种机械性疾病也是一种炎症性疾病WhyHasitTakenSoLongtoRecognizethatOsteoarthritisisanInflammatoryDisease?COLLAGENIIAGGRECANAvascular,Aneural,Alymphatic无血管,无神经,无淋巴NORMALCARTILAGE正常软骨Thenon-vascularizeddamagedcartilagecannotrespondbyausualinflammatoryresponse.无血管损伤后的软骨不能应答正常的炎症反应CollagenfibrildegradationAggrecanswellingthenloss胶原纤维退化,聚集蛋白聚糖肿胀后消失OSTEOARTHRITICCARTILAGE关节炎软骨为什么人们花了这么久才认识到骨关节炎是一种炎症性疾病？SignsofInflammationinOsteoarthritisareFrequentWhenSensitiveToolsareUsed•Frequenteffusions频繁关节积液Song2008:78%byultrasoundand81%byMRIin超声检测78%和MRI检测81%Tarhan2003:70%byultrasound,80%byMRI超声检测70%和MRI检测80%•Frequentsynovialthickening频繁滑膜增厚Tarhan2003:34%byultrasound,50%byMRI超声检测34%和MRI检测50%•Frequentpopliteal(Baker’s)cysts频繁腘窝囊肿（Baker囊肿）Tarhan2003:40%byultrasound,35%byMRI超声检测40%和MRI检测35%References参考文献:Songetal.AnnRheumDis2008;67(1):19-25Tarhanetal.ClinRheumatol2003;22(3):181-8当使用一些敏感的检测手段时,骨关节炎的炎症指标就会频繁出现SignsofInflammationinOsteoarthritisarealsoFrequentataMolecularLevel•Innateimmunityistriggered先天免疫被激活•HighexpressionandactivationofComplement补体激活及高表达•ActivationbyCrystals:Calciumpyrophosphatedihydrate,basiccalciumphosphateanduricacidcrystals被晶体激活：二水焦磷酸钙化合物,碱性磷酸钙和尿酸结晶•LevelsofseveralInflammatoryMediatorsarehigherinOAthanhealthyseraandsynovialfluidOA患者血清及滑夜中一些炎症介质的水平高于正常人•PresenceofMacrophagesinsynovium滑膜中存在巨噬细胞References参考文献:BerenbaumF.OsteoarthritisCartilage2013;21(1):16-21Denoble,Krausetal.ProcNatlAcadSciUSA2011;108(5):2088-93在分子水平上，骨关节炎的炎症指标同样也会频繁出现SignsofInflammationinOsteoarthritiscanbeDemonstratedinvivoby99mTc-EC20‘FolateScans’在分子水平上，骨关节炎的炎症指标同样也会频繁出现•TheFolateReceptorisexpressedonactivatedbutnotrestingmacrophages(LowPS,etal.AccChemRes2008;41(1):120-9).活化非静息的巨噬细胞能够表达叶酸受体Anewimagingagent--99mTc-EC20(Etarfolatide),canidentifyactivatedmacrophagesinvivo.一个新型成像试剂--99mTc-EC20(Etarfolatide),能够识别体内活化的巨噬细胞99mTc-EC20(Etarfolatide)consistsofthevitaminfolateconjugatedto99mTcviaachelatingmoiety.一个新型成像试剂--99mTc-EC20(Etarfolatide),能够识别体内活化的巨噬细胞TcO99mNuclearmedicineradiopharmaceuticalforIVinjectionResults–SPECT-CT99mTc-EC20IdentifiesActivatedMacrophagesinOAJoints结果–SPECT（单光子发...
