前交叉韧带损伤对润滑素代谢的影响以及在动物模型中抑制肿瘤坏死因子α对软骨保护的作用。
The impact of anterior cruciate ligament injury on lubricin metabolism and the effect of inhibiting tumor necrosis factor alpha on chondroprotection in an animal model.
作者信息
Elsaid K A, Machan J T, Waller K, Fleming B C, Jay G D
机构信息
Brown University, Providence, Rhode Island, USA.
出版信息
Arthritis Rheum. 2009 Oct;60(10):2997-3006. doi: 10.1002/art.24800.
OBJECTIVE
To examine the effects of anterior cruciate ligament transection (ACLT) in a rat model on lubricin metabolism and its relationship to markers of inflammation and cartilage damage, and to determine whether blocking the metabolic effects of tumor necrosis factor alpha (TNFalpha) by etanercept increases the chondroprotection provided by lubricin.
METHODS
Unilateral ACLT was performed in Lewis rats. Levels of lubricin, TNFalpha, interleukin-1beta (IL-1beta), and sulfated glycosaminoglycans (sGAG) in synovial fluid (SF) lavage specimens and synovial tissue lubricin gene expression were evaluated at 1 week and 4 weeks following ACLT. Histologic evaluation of articular cartilage included staining with lubricin-specific monoclonal antibody 9G3 and Safranin O. The percentage of lubricin staining on the surface of articular cartilage in weight-bearing areas was estimated by digital imaging. Blocking of TNFalpha was performed using etanercept, which was administered subcutaneously at a dose of 0.5 mg/kg around the ACL-transected joints, using different dosing strategies. The ACL-transected and contralateral joints of these rats were harvested 4 weeks following surgery.
RESULTS
Four weeks following ACLT, SF lubricin concentrations and the percentage of cartilage surface lubricin staining were significantly lower in the injured joints compared with the contralateral joints. A significant decrease in synovial tissue lubricin gene expression was associated with elevated TNFalpha and IL-1beta concentrations in SF lavage samples. With all of the etanercept treatment strategies, blocking of TNFalpha significantly increased the amount of lubricin bound to cartilage, coupled with a significant decrease in sGAG release. However, changes in the concentrations of lubricin in SF were variable.
CONCLUSION
Blocking TNFalpha resulted in a chondroprotective effect, exemplified by increased lubricin deposition on articular cartilage and a decrease in sGAG release from articular cartilage in an animal model of posttraumatic arthritis.
目的
研究大鼠前交叉韧带横断（ACLT）模型中润滑素代谢的变化及其与炎症标志物和软骨损伤的关系，并确定通过依那西普阻断肿瘤坏死因子α（TNFα）的代谢作用是否能增强润滑素对软骨的保护作用。
方法
对Lewis大鼠进行单侧ACLT。在ACLT术后1周和4周，评估滑膜液（SF）灌洗标本中润滑素、TNFα、白细胞介素-1β（IL-1β）和硫酸化糖胺聚糖（sGAG）的水平以及滑膜组织中润滑素基因的表达。关节软骨的组织学评估包括用润滑素特异性单克隆抗体9G3和番红O染色。通过数字成像估计负重区域关节软骨表面润滑素染色的百分比。使用依那西普阻断TNFα，采用不同给药策略，以0.5mg/kg的剂量在ACLT切断的关节周围皮下给药。这些大鼠在手术后4周收获ACLT切断侧和对侧关节。
结果
ACLT术后4周，与对侧关节相比，损伤关节的SF润滑素浓度和软骨表面润滑素染色百分比显著降低。滑膜组织润滑素基因表达的显著降低与SF灌洗样本中TNFα和IL-1β浓度的升高有关。采用所有依那西普治疗策略，阻断TNFα均显著增加了与软骨结合的润滑素量，同时sGAG释放显著减少。然而，SF中润滑素浓度的变化是可变的。
结论
在创伤后关节炎动物模型中，阻断TNFα产生了软骨保护作用，表现为关节软骨上润滑素沉积增加以及关节软骨sGAG释放减少。
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