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首页> 外文期刊>Journal of orthopaedic research >Dual transduction of insulin-like growth factor-I and interleukin-1 receptor antagonist protein controls cartilage degradation in an osteoarthritic culture model.
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Dual transduction of insulin-like growth factor-I and interleukin-1 receptor antagonist protein controls cartilage degradation in an osteoarthritic culture model.

机译：胰岛素样生长因子-I和白介素-1受体拮抗剂蛋白的双重转导可控制骨关节炎培养模型中的软骨降解。

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This study evaluated the potential of gene induced synoviocyte expression of a combination of insulin-like growth factor-I (AdIGF-I) and interleukin-1 receptor antagonist protein (AdIL-1Ra) to control articular cartilage degradation in vitro. Cartilage explants and synovial membrane were harvested from young mature horses. Synovial monolayers were established and either (1) maintained as untransduced controls; (2) transduced with AdIGF-I at 200 MOI in 500mul serum-free medium; (3) transduced with AdIL-1Ra at 100 MOI; or (4) transduced with a combination of AdIGF-I (200 MOI) and AdIL-1Ra (100 MOI). Following transduction, cartilage explants were exposed to the synovial monolayer medium using co-culture inserts. Cultures were maintained for 6days in either serum-free medium or medium containing 10ng/ml recombinant human interleukin-1beta. At termination, synovial cell RNA was isolated for real-time PCR analysis, and cartilage explants were collected for H&E and toluidine blue staining, immunohistochemistry for type II collagen and IGF-I, in situ localization of IGF-I and type II collagen gene expression, and biochemical assays. Synovial monolayers were readily transduced with both AdIGF-I and AdIL-1Ra. IGF-I and IL-1Ra protein were secreted at beneficial levels throughout the experiment, having peak concentrations of 94.6ng/ml and 33.0ng/ml, respectively. Transduction with IGF-I promoted cartilage production of proteoglycan and type II collagen, suggesting a beneficial role for healing injured cartilage. Transduction with IL-1Ra decreased the synovial expression of IL-1alpha and IL-1beta and matrix metalloproteinases, indicating a mechanism for prevention of matrix degradation. The beneficial effects of the combination of anabolic growth factors and catabolic blockers were evident in improved preservation of proteoglycan content of cartilage explants exposed to the depleting effects of IL-1. These results show that gene therapy combining anabolic growth factors to stimulate matrix synthesisand catabolic blockers to prevent matrix degradation by IL-1, protects and causes partial restoration of cartilage matrix, and suggest a potential benefit of combination gene therapy for cartilage healing.
机译：这项研究评估了基因诱导的滑膜细胞表达的胰岛素样生长因子-I（AdIGF-I）和白介素-1受体拮抗剂蛋白（AdIL-1Ra）的组合在体外控制关节软骨降解的潜力。从年轻的成熟马中收获软骨外植体和滑膜。建立滑膜单层，并且（1）保持为未转导的对照; （2）在500 mul无血清培养基中以200 MOI的AdIGF-I进行转导; （3）以100 MOI的AdIL-1Ra进行转导;或（4）用AdIGF-1（200 MOI）和AdIL-1Ra（100 MOI）的组合转导。转导后，使用共培养插入物将软骨外植体暴露于滑膜单层培养基。将培养物在无血清培养基或含有10ng / ml重组人白介素1β的培养基中维持6天。终止时，分离滑膜细胞RNA进行实时PCR分析，收集软骨外植体用于H＆E和甲苯胺蓝染色，II型胶原和IGF-I的免疫组织化学，IGF-I的原位定位和II型胶原基因表达以及生化分析。滑膜单层很容易用AdIGF-1和AdIL-1Ra转导。在整个实验过程中，IGF-I和IL-1Ra蛋白以有益水平分泌，其峰值浓度分别为94.6ng / ml和33.0ng / ml。 IGF-I的转导促进了蛋白聚糖和II型胶原的软骨生成，提示了对受伤的软骨进行愈合的有益作用。 IL-1Ra的转导降低了IL-1alpha和IL-1beta和基质金属蛋白酶的滑膜表达，表明了预防基质降解的机制。合成代谢生长因子和分解代谢阻滞剂的组合的有益作用在暴露于IL-1耗竭作用的软骨外植体的蛋白聚糖含量得到更好的保存方面得到了明显体现。这些结果表明基因治疗结合同化生长因子刺激基质合成，而分解代谢阻滞剂阻止IL-1降解基质，保护并引起软骨基质部分恢复，并提出联合基因治疗对软骨愈合的潜在益处。

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