Superficial Zone Protein (SZP) and Arthritis

关节软骨是位于长骨末端的一种无血管、无神经的异质性组织。它 ）执行至少两个功能。首先，它提供了一个几乎无摩擦的表面， 关节骨其次，它将载荷从软骨表面传递到软骨下骨。的能力 执行这两种功能取决于关节软骨表层的完整性及其 当两个相对的表面彼此相对移动时，抗磨损。一种叫做表层的糖蛋白 蛋白质（SZP）已从软骨组织中纯化。SZP特异性抗体显示该分子是 局限于关节软骨的表层，组织的中层和深层没有。 测序数据和生化实验表明SZP与润滑素相同，润滑素是SZP的主要代谢产物。 滑液中的润滑糖蛋白。SZP/润滑素的边界润滑功能可能涉及 SZP与软骨表面其他大分子的结合，因此SZP的结合特性 将被调查。SZP与Vitronectin的同源性提示SZP可能具有细胞粘附性 因此，将研究SZP增强或抑制细胞粘附的能力。一组单克隆 抗体将用于夹心ELISA以测量滑液中SZP的浓度。滑膜 将检测来自OA患者和器官供体的液体，以确定这些液体中SZP的浓度 与这些个体的软骨损伤程度相关。软骨细胞来源于 将关节炎软骨在培养物中合成SZP的能力与软骨细胞的合成能力进行比较 从捐赠者的软骨中SZP在软骨表面的润滑性质和位置表明这一点 分子是软骨保护性的，并且有益于软骨的体内平衡。未来这些研究 应该有助于提供一个合理的框架，以改善关节润滑和运动，在数以百万计的 患有关节炎的人。

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.