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STR/ort Mice, a Model for Spontaneous Osteoarthritis, Exhibit Elevated Levels of Both Local and Systemic Inflammatory Markers

机译:STR / ort小鼠,一种自发性骨关节炎的模型,其局部和全身炎症标志物的水平均升高

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Osteoarthritisisacommonjointdiseasethatcurrentlylacksdisease-modifyingtreatments.Developmentoftherapeuticagentsforosteoarthritisrequiresbetterunderstandingofthediseaseandcost-effectiveinvivomodelsthatmimicthehumandisease.Here,weanalyzedthejointsofSTR/ortmice,amodelforspontaneousosteoarthritis,forlevelsofinflammatoryandoxidativestressmarkersandmeasuredserumcytokinestocharacterizethelocalandsystemicinflammatorystatusofthesemice.Markersoflow-gradeinflammatoryandoxidativestress#8212;RAGE,AGE,S100A4,andHMGB1#8212;wereevaluatedthroughimmunohistochemistry.Ofthese,AGEandHMGB1levelswereelevatedstronglyinhyperplasticsynovium,cartilage,meniscus,andligamentsinthejointsofSTR/ortmicecomparedwithCBAmice,anosteoarthritis-resistantmousestrain.Theseincreases(particularlyinthesynovium,meniscus,andligaments)correlatedwithincreasedhistopathologicchangesinthecartilage.SerumanalysisshowedhigherconcentrationsofseveralcytokinesincludingIL1#946;,IL12p70,MIP1#946;,andIL5inSTR/ortmice,andthesechangescorrelatedwithworsenedjointmorphology.TheseresultsindicatethatSTR/ortmiceexhibitedlocalandsystemicproinflammatoryconditions,bothofwhicharepresentinhumanosteoarthritis.Therefore,theSTR/ortmousemodelappearstobeaclinicallyrelevantandcost-effectivesmallanimalmodelfortestingosteoarthritistherapeutics.
机译:Osteoarthritisisacommonjointdiseasethatcurrentlylacksdisease-modifyingtreatments.Developmentoftherapeuticagentsforosteoarthritisrequiresbetterunderstandingofthediseaseandcost-effectiveinvivomodelsthatmimicthehumandisease.Here,weanalyzedthejointsofSTR / ortmice,amodelforspontaneousosteoarthritis,forlevelsofinflammatoryandoxidativestressmarkersandmeasuredserumcytokinestocharacterizethelocalandsystemicinflammatorystatusofthesemice.Markersoflow-gradeinflammatoryandoxidativestress#8212; RAGE,AGE,S100A4,andHMGB1#8212; wereevaluatedthroughimmunohistochemistry.Ofthese,AGEandHMGB1levelswereelevatedstronglyinhyperplasticsynovium,软骨,半月板,andligamentsinthejointsofSTR / ortmicecomparedwithCBAmice,anosteoarthritis-这些增加(尤其是滑囊炎,半月板和韧带的增加)与软骨组织病理学变化的增加有关。血清分析显示几种细胞因子的浓度较高,包括IL1#946; IL12p70,MIP1#946;以及与STR /小鼠相关的IL5。结果表明,STR / ortice表现出局部和全身性促炎性条件,bothof代表了人类骨关节炎。因此,STR / ortmouse模型在临床上似乎是相关的,并且具有成本效益,可用于测试骨关节炎的小动物模型。

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