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Adiponectin attenuates osteolysis in aseptic loosening of total hip replacements

机译:脂联素在无菌性全髋关节置换术中减轻骨溶解

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Joint replacements have a longer durability in patients with high serum levels of adiponectin (APN) than in patients with low levels. We aimed to characterize the unknown pathophysiological effects of APN on wear particle-induced inflammation, apoptosis and osteolysis. Immunohistochemistry was performed to detect APN, its receptors and apoptosis in patients with and without aseptic loosening. Additionally, APN knockout mouse studies and pharmacological intervention of APN were performed in an established calvarial mouse model. Osteolysis and inflammation were quantified by histomorphometry and microcomputed tomography, apoptosis by immunohistochemistry and TUNEL assay. In a cell culture model, human monocyte-derived macrophages were incubated with or without metal wear debris particles and partially treated with APN. Expression of APN, AdipoR1 and calreticulin in specimens from patients with aseptic loosening were significantly higher than in patients without aseptic loosening. Administration of APN in mice significantly reduced wear particle-induced inflammation, osteolysis and the number of caspase-3-positive macrophages. The cell culture model showed that APN leads to significantly lower values of TNF-α. These findings support a prominent role of APN in the development of particle-induced osteolysis and APN may be therapeutically useful in patients with aseptic loosening.
机译:血清脂联素(APN)水平高的患者的关节置换术比低水平的患者具有更长的耐久性。我们旨在表征APN对磨损颗粒诱导的炎症,细胞凋亡和溶骨的未知病理生理影响。进行免疫组织化学检测在有和没有无菌性松弛的患者中APN,其受体和细胞凋亡。此外,在已建立的颅盖小鼠模型中进行了APN基因敲除小鼠研究和APN的药理干预。骨溶解和炎症通过组织形态计量学和微计算机断层扫描进行定量,通过免疫组织化学和TUNEL测定进行凋亡。在细胞培养模型中,将人类单核细胞衍生的巨噬细胞与或不与金属磨损碎片一起孵育,并用APN进行部分处理。无菌性松动患者的标本中APN,AdipoR1和钙网蛋白的表达显着高于无无菌性松动患者的标本。在小鼠中施用APN可显着减少磨损颗粒诱导的炎症,骨溶解和caspase-3阳性巨噬细胞的数量。细胞培养模型表明,APN导致TNF-α值明显降低。这些发现支持APN在颗粒诱导的骨溶解发展中的重要作用,并且APN在无菌性松动患者中可能具有治疗作用。

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