Superficial Zone Protein (SZP) and Arthritis

描述（由申请人提供）：关节软骨是位于长骨末端的无血管、神经和异质组织。它至少执行两个功能。首先，它为两个关节骨骼的运动提供了几乎无摩擦的表面。其次，它将负载从软骨表面传递到软骨下骨。执行这两种功能的能力取决于关节软骨表层的完整性及其在两个相对表面相互移动时抵抗磨损的能力。从软骨组织中纯化出一种称为浅表带蛋白（SZP）的糖蛋白。SZP的特异性抗体显示该分子仅存在于关节软骨的表层，而不存在于组织的中层和深层。测序数据和生化实验表明SZP与滑液中主要的润滑糖蛋白润滑素相同。SZP/润滑素的边界润滑功能可能涉及到SZP与软骨表面其他大分子的结合，因此我们将研究SZP的结合特性。SZP与玻璃体连接蛋白的同源性表明SZP可能具有细胞粘附特性，因此将对SZP增强或抑制细胞粘附的能力进行研究。一组单克隆抗体将用于夹心ELISA来测量滑液中SZP的浓度。将检测OA患者和器官供体的滑液，以确定这些液体中SZP的浓度是否与这些个体的软骨损伤程度相关。从关节炎软骨中提取的软骨细胞合成SZP的能力将与从供体软骨中提取的软骨细胞的合成能力进行比较。SZP在软骨表面的润滑特性和位置表明该分子具有软骨保护作用，有利于软骨的内稳态。在未来，这些研究应该有助于提供一个合理的框架，以改善数百万关节炎患者的关节润滑和运动。

DESCRIPTION (provided by applicant): Articular cartilage is an avascular, aneural and heterogeneous tissue at the ends of the long bones. It performs at least two functions. First, it provides a nearly frictionless surface for the movement of two articulating bones. Second, it transmits loads from the cartilage surface to the subchondral bone. The ability to perform both functions depends on the integrity of the superficial layer of articular cartilage and its ability to resist wear as two opposing surfaces move against one another. A glycoprotein called the superficial zone protein (SZP) has been purified from cartilage tissue. Antibodies specific for SZP show the molecule is restricted to the surface layer of articular cartilage and absent from the middle and deep layers of the tissue. Sequencing data and biochemical experiments suggest SZP is identical to lubricin, which is the major lubricating glycoprotein in synovial fluid. The boundary lubricant function of SZP/lubricin is likely to involve the binding of SZP to other macromolecules at the cartilage surface, therefore the binding properties of SZP will be investigated. The homology of SZP to vitronectin suggests that SZP may have cell adhesive properties, so the ability of SZP to enhance or inhibit cell adhesion will be studied. A panel of monoclonal antibodies will be used in a sandwich ELISA to measure the concentration of SZP in synovial fluid. Synovial fluid from OA patients and organ donors will be tested to determine if the concentration of SZP in these fluids correlates with the degree of cartilage damage in these individuals. The ability of chondrocytes derived from arthritic cartilage to synthesize SZP in culture will be compared to the synthetic capacity of chondrocytes from donor cartilage. The lubricating properties and location of SZP at the cartilage surface suggest this molecule is chondroprotective and beneficial for the homeostasis of cartilage. In the future these studies should help provide a rational framework for improving joint lubrication and movement in the millions of individuals who suffer from arthritis.