Superficial Zone Protein (SZP) and Arthritis

浅层区蛋白 (SZP) 和关节炎

• 批准号: 6824133
• 负责人: THOMAS M SCHMID
• 金额: $ 24.99万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6824133
• 关键词: SDS polyacrylamide gel electrophoresis; arthritis; articular cartilage; cell adhesion molecules; chondrocytes; clinical research; enzyme linked immunosorbent assay; glycoprotein biosynthesis; glycoproteins; human tissue; immunocytochemistry; in situ hybridization; laboratory rabbit; macromolecule; membrane proteins; monoclonal antibody; osteoarthritis; pathologic process; protein binding; protein isoforms; protein structure function; rheumatoid arthritis; synovial fluid; synovial membrane; tissue /cell culture; western blottings

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.

描述（由申请人提供）：关节软骨是长骨头末端的一种无血管，动脉和异质组织。它执行至少两个功能。首先，它为两个铰接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面的完整性及其抵抗磨损的能力，因为两个相对的表面相互对抗。一种称为浅层区蛋白（SZP）的糖蛋白已从软骨组织中纯化。 SZP特异的抗体表明该分子仅限于关节软骨的表面层，并且没有组织的中层和深层。测序数据和生化实验表明SZP与润滑剂相同，这是滑液中主要的润滑糖蛋白。 SZP/润滑剂的边界润滑剂功能可能涉及软骨表面上SZP与其他大分子的结合，因此将研究SZP的结合特性。 SZP对玻璃体蛋白的同源性表明SZP可能具有细胞粘附特性，因此将研究SZP增强或抑制细胞粘附的能力。一组单克隆抗体将在三明治ELISA中使用，以测量滑液中SZP的浓度。将测试来自OA患者和器官供体的滑液，以确定这些流体中SZP的浓度是否与这些个体软骨损伤程度相关。从关节炎软骨中衍生出培养物中SZP的软骨细胞的能力将与供体软骨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是软骨保护性的，对软骨的体内平衡有益。将来，这些研究应有助于提供一个合理的框架，以改善数百万患有关节炎的人的关节润滑和运动。