The impact of anterior cruciate ligament injury on lubricin metabolism and the effect of inhibiting tumor necrosis factor α on chondroprotection in an animal model

Abstract

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. 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. 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. 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.