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首页> 外文期刊>Osteoarthritis and cartilage >Local gene delivery of heme oxygenase-1 by adeno-associated virus into osteoarthritic mouse joints exhibiting synovial oxidative stress
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Local gene delivery of heme oxygenase-1 by adeno-associated virus into osteoarthritic mouse joints exhibiting synovial oxidative stress

机译：腺相关病毒将血红素加氧酶-1的局部基因传递到表现出滑膜氧化应激的骨关节炎小鼠关节中

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Objective: To evaluate the role of synovial oxidative stress on joint pathology in a spontaneous mouse model of osteoarthritis (OA) by intra-articular (IA) delivery of recombinant adeno-associated virus (rAAV) expressing anti-oxidant protein heme oxygenase-1 (HO-1). Methods: Joint transduction by rAAV vectors was evaluated with serotype 1, 2, 5 and 8 capsids carrying LacZ gene administered by IA injections into STR/ort mice. Transduced cell types were identified by ??-galactosidase staining in sectioned joints. Effect of oxidative stress on AAV transduction of primary synoviocytes in vitro was quantitated by fluorescence-activated cell sorting (FACS) analysis. In vivo, the efficacy of rAAV1/HO-1 was tested by IA administration into STR/ort mice followed by histopathological scoring of cartilage. Levels of 3-nitrotyrosine (3-NT) and HO-1 were assessed by immunohistochemistry (IHC) of joint sections. Results: Administration of a rAAV1 based vector into OA mouse joints resulted in transduction of the synovium, joint capsule, adipocytes and skeletal muscle while none of the serotypes showed significant cartilage transduction. All OA joints exhibited significantly elevated levels of oxidative stress marker, 3-NT, in the synovium compared to OA-resistant CBA-strain of mice. In vitro studies demonstrated that AAV transgene expression in primary synoviocytes was augmented by oxidative stress induced by H2O2 and that a rAAV expressing HO-1 reduced the levels of oxidative stress. In vivo, HO-1 was increased in the synovium of STR/ort mice. However, delivery of rAAV1/HO-1 into OA joints did not reduce cartilage degradation. Conclusions: AAV-mediated HO-1 delivery into OA joints during active disease was not sufficient to improve cartilage pathology in this model. ? 2012 Osteoarthritis Research Society International.
机译：目的：通过关节内（IA）递送表达抗氧化蛋白血红素加氧酶-1（rAAV）的重组腺相关病毒（rAAV），评估滑膜氧化应激对自发性骨关节炎（OA）小鼠模型关节病理的作用。 HO-1）。方法：用携带LacZ基因的血清型1、2、5和8衣壳，通过IA / STR小鼠IA注射，评估rAAV载体的联合转导。通过β-半乳糖苷酶染色在关节切片中鉴定出转导的细胞类型。通过荧光激活细胞分选（FACS）分析定量了氧化应激对原代滑膜细胞AAV转导的影响。在体内，通过对STR / ort小鼠IA施用IA，然后对软骨进行组织病理学评分，来测试rAAV1 / HO-1的功效。通过关节切片的免疫组织化学（IHC）评估3-硝基酪氨酸（3-NT）和HO-1的水平。结果：在OA小鼠关节中施用基于rAAV1的载体可导致滑膜，关节囊，脂肪细胞和骨骼肌的转导，而所有血清型均未显示出明显的软骨转导。与OA抗性的CBA株相比，滑膜中的所有OA关节均表现出显着升高的氧化应激标记物3-NT水平。体外研究表明，H2O2诱导的氧化应激增强了初级滑膜细胞中AAV转基因的表达，表达HO-1的rAAV降低了氧化应激的水平。在体内，HO-1在STR / ort小鼠的滑膜中增加。但是，将rAAV1 / HO-1递送至OA关节并不能减少软骨降解。结论：活动性疾病期间AAV介导的HO-1传递至OA关节不足以改善该模型中的软骨病理。 ？ 2012年国际骨关节炎研究学会。

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