The impact of early intra-articular administration of interleukin-1 receptor antagonist on lubricin metabolism and cartilage degeneration in an anterior cruciate ligament transection model.

The impact of early intra-articular administration of interleukin-1 receptor antagonist on lubricin metabolism and cartilage degeneration in an anterior cruciate ligament transection model.
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DOI:
10.1016/j.joca.2014.09.006
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发表时间:
2015-01
影响因子:
7
通讯作者:
Jay, G. D.
Jay, G. D.
中科院分区:
医学2区
文献类型:
--
作者:
Elsaid, K. A.;Zhang, L.;Shaman, Z.;Patel, C.;Schmidt, T. A.;Jay, G. D.

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研究关节内白细胞介素-1受体拮抗剂(IL-1 ra)治疗对大鼠前交叉韧带横断(ACLT)后润滑素生物合成的影响,并评估IL-1 ra和重组人润滑素(rhPRG 4)联合治疗对软骨细胞凋亡和MMP-13表达的影响。在雄性刘易斯大鼠中进行ACLT。用PBS或IL-1 ra处理动物(每组n=36)。在ACLT后第1、3、5和7天使用阿那白滞素(150 mg/ml; 40 µl)进行IL-1 ra关节内给药。在第3周和第5周,处死动物并分离RNA。组织学分析包括润滑素、番红0和H&E。在5周时测定润滑素滑液(SF)灌洗浓度。在ACLT后第7天用PBS、IL-1 ra(75 mg/ml; 40 μl)、rhPRG 4(200 μg/ml; 40μl)或IL-1 ra + rhPRG 4(75 mg/ml + 200 μg/ml; 40μl)(每组n=6)的单次注射处理ACLT动物,并在第5周探测软骨中裂解的半胱天冬酶-3和MMP-13。IL-1 ra处理改善了润滑素表达(p<0.001),并且IL-1 ra处理组中的润滑素SF灌洗液浓度高于PBS处理组(p=0.005)。与PBS相比,IL-1 ra治疗降低了软骨和滑膜评分(p<0.001)。与单独处理相比,IL-1 ra和rhPRG 4协同作用以减少半胱天冬酶-3阳性软骨细胞(p<0.001)和MMP-13染色。IL-Ira治疗保留了ACLT后的润滑素,并且IL-Ira + rhPRG 4的组合治疗可协同作用以减少软骨软骨松解。
Study the impact of intra-articular interleukin-1 receptor antagonist (IL-1 ra) treatment on lubricin biosynthesis following anterior cruciate ligament transection (ACLT) in the rat and evaluate the effect of combined IL-1 ra and recombinant human lubricin (rhPRG4) treatments on chondrocyte apoptosis and MMP-13 expression. ACLT was performed in male Lewis rats. Animals were treated with PBS or IL-1 ra (n=36 in each group). IL-1 ra intra-articular dosing was performed on days 1, 3, 5 and 7 following ACLT using Anakinra (150 mg/ml; 40 µl). At 3 and 5 weeks, animals were sacrificed and RNA was isolated. Histological analyses included lubricin, Safranin O and H&E. Lubricin synovial fluid (SF) lavage concentrations were determined at 5 weeks. ACLT animals were treated with a single injection of PBS, IL-1 ra (75 mg/ml; 40 µl), rhPRG4 (200 µg/ml; 40µl), or IL-1 ra + rhPRG4 (75 mg/ml + 200 µg/ml; 40µl) (n=6 in each group) on day 7 following ACLT and cartilage was probed for cleaved caspase-3 and MMP-13 at 5 weeks. IL-1 ra treatment improved lubricin expression (p<0.001) and lubricin SF lavage concentrations in the IL-1 ra treated group was higher (p=0.005) than the PBS treated group. IL-1 ra treatment reduced cartilage and synovial scores (p<0.001) compared to PBS. IL-1 ra and rhPRG4 acted synergistically to reduce caspase-3 positive chondrocytes (p<0.001) and MMP-13 staining compared to individual treatments. IL-1 ra treatment preserved lubricin following ACLT and a combined treatment of IL-1 ra + rhPRG4 may act synergistically to reduce cartilage catabolism.
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