Superficial Zone Protein (SZP) and Arthritis

关节软骨是位于长骨末端的一种无血管、神经和异质组织。它 )至少执行两个函数。首先，它为两个物体的运动提供了一个几乎无摩擦的表面 接合的骨头。其次，它将载荷从软骨表面传递到软骨下骨。一种能力 执行这两种功能取决于关节软骨浅层的完整性和它的能力 当两个相对的表面相互运动时，可以抵抗磨损。一种叫做表面区的糖蛋白 从软骨组织中提纯了蛋白质(SZP)。针对SZP的抗体显示该分子是 仅限于关节软骨的表层，而不存在于该组织的中深层。 测序数据和生化实验表明，SZP与润滑油相同，而润滑油是主要的 滑液中的润滑糖蛋白。SZP/润滑剂的边界润滑剂功能可能涉及 SZP与软骨表面其他大分子的结合，从而影响SZP的结合性能 将会被调查。SZP与Vitronectin的同源性提示SZP可能具有细胞黏附作用 因此，我们将研究SZP增强或抑制细胞黏附的能力。一组单克隆性 抗体将用于夹心ELISA法测定滑液中SZP的浓度。滑膜 将对来自OA患者和器官捐赠者的液体进行测试，以确定这些液体中SZP的浓度 与这些人的软骨损伤程度有关。软骨细胞来源的能力 关节软骨在培养中合成SZP的能力将与软骨细胞的合成能力进行比较 来自供体软骨。SZP的润滑性能和在软骨表面的位置表明了这一点 分子对软骨具有保护作用，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人的关节润滑和运动提供一个合理的框架 患有关节炎的个人。

Articular cartilage is an avascular, aneural and heterogeneous tissue at the ends of the long bones. It )erforms 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.