Thorson Chase, Galicia Kevin, Burleson Andrew, Bouchard Olivia, Hoppensteadt Debra, Fareed Jawed, Hopkinson William
1 Department of Pathology, Loyola University Medical Center, Maywood, IL, USA.
2 Department of Orthopedics, Loyola University Medical Center, Maywood, IL, USA.
Clin Appl Thromb Hemost. 2019 Jan-Dec;25:1076029619828113. doi: 10.1177/1076029619828113.
Osteoarthritis, a degenerative disease of the joints, is the most common form of arthritis in the knee. Total joint arthoplasty is a commonly used treatment for joint degeneration and osteoarthritis, and due to these factors, TJA for hip and knee joints is projected to grow by 137% and 601% between 2005 and 2030. Matrix metalloproteases are enzymes found in the extracellular matrix that cleave matrix components. Normally MMPs are downregulated in tissues by Tissue Inhibitors of Metalloproteases, or TIMPs. The relative concentration of TIMPs also may denote some of the activity of the MMPs found in serum. Lubricin (proteoglycan 4) is a molecule found in the synovial fluid that protects joints by dissipating strain energy during locomotion. Lubricin synovial fluid concentration is also diminished in many patients with osteoarthritis, but not all. Given the importance of these three sets of molecules, our lab investigated the correlation between circulating lubricin, MMP levels and TIMPs levels. Blood plasma samples were obtained from de-identified subjects undergoing total joint arthroplasty at Loyola University Medical Center and the University of Utah. Normal blood plasma from pooled healthy individuals served as a control. We analyzed biomarker levels in plasma using ELISA. Our data show that MMP-1 and 9 were increased in TJA patients compared to normal controls, while MMP-2 and 13 were decreased. We also found decreased lubricin and tissue factor in surgical patients relative to controls. These data support the idea that lubricin is vital in protecting the synovial joint and that MMPs play a complex role in the destruction of the joint.
骨关节炎是一种关节退行性疾病,是膝关节中最常见的关节炎形式。全关节置换术是治疗关节退变和骨关节炎常用的方法,由于这些因素,预计2005年至2030年间髋膝关节的全关节置换术将分别增长137%和601%。基质金属蛋白酶是存在于细胞外基质中可裂解基质成分的酶。正常情况下,基质金属蛋白酶在组织中由金属蛋白酶组织抑制剂(TIMP)下调。TIMP的相对浓度也可能表示血清中基质金属蛋白酶的一些活性。润滑素(蛋白聚糖4)是一种存在于滑液中的分子,通过在运动过程中消散应变能量来保护关节。许多骨关节炎患者滑液中的润滑素浓度也会降低,但并非所有患者都是如此。鉴于这三组分子的重要性,我们实验室研究了循环润滑素、基质金属蛋白酶水平和TIMP水平之间的相关性。血浆样本取自洛约拉大学医学中心和犹他大学接受全关节置换术的身份不明的受试者。来自健康个体混合的正常血浆用作对照。我们使用酶联免疫吸附测定法分析血浆中的生物标志物水平。我们的数据显示,与正常对照组相比,全关节置换术患者的基质金属蛋白酶-1和-9增加,而基质金属蛋白酶-2和-13减少。我们还发现手术患者相对于对照组的润滑素和组织因子减少。这些数据支持了润滑素在保护滑膜关节中至关重要以及基质金属蛋白酶在关节破坏中起复杂作用的观点。