Superficial Zone Protein (SZP) and Arthritis

描述(申请人提供)：关节软骨是位于长骨末端的一种无血管的、神经的和异质的组织。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一个几乎无摩擦的表面。其次，它将载荷从软骨表面传递到软骨下骨。实现这两种功能的能力取决于关节软骨表层的完整性，以及当两个相对的表面相互运动时，关节软骨抵抗磨损的能力。从软骨组织中提纯了一种名为表面区蛋白(SZP)的糖蛋白。针对SZP的抗体表明，SZP分子仅限于关节软骨的表层，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与滑液中的主要润滑糖蛋白润滑素相同。SZP/LUSING的边界润滑剂作用可能涉及SZP与软骨表面其他大分子的结合，因此SZP的结合特性有待研究。SZP与Vitronectin的同源性表明SZP可能具有细胞黏附特性，因此SZP促进或抑制细胞黏附的能力将被研究。一组单抗将用于夹心ELISA法测定滑液中SZP的浓度。将对来自OA患者和器官捐赠者的滑液进行测试，以确定这些液中SZP的浓度是否与这些人的软骨损伤程度有关。来自关节炎软骨的软骨细胞在培养中合成SZP的能力将与来自供体软骨的软骨细胞的合成能力进行比较。SZP的润滑性能和在软骨表面的定位表明，该分子具有软骨保护作用，有利于软骨的动态平衡。在未来，这些研究应该有助于为改善数百万关节炎患者的关节润滑和运动提供一个合理的框架。

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.