Superficial Zone Protein (SZP) and Arthritis

浅层区蛋白 (SZP) 和关节炎

• 批准号: 6929227
• 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/6929227
• 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）：关节软骨是长骨末端的无血管、无神经和异质组织。它至少执行两个功能。首先，它为两个关节骨的运动提供了几乎无摩擦的表面。其次，它将载荷从软骨表面传递到软骨下骨。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。一种称为表面区蛋白（SZP）的糖蛋白已从软骨组织中纯化出来。 SZP 特异性抗体显示该分子仅限于关节软骨的表层，而在组织的中层和深层不存在。测序数据和生化实验表明，SZP 与润滑素相同，润滑素是滑液中的主要润滑糖蛋白。 SZP/lubricin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，因此将研究SZP的结合特性。 SZP与玻连蛋白的同源性表明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。一组单克隆抗体将用于夹心 ELISA 测量滑液中 SZP 的浓度。将对 OA 患者和器官捐献者的滑液进行测试，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。将来自关节炎软骨的软骨细胞在培养物中合成SZP的能力与来自供体软骨的软骨细胞的合成能力进行比较。 SZP 的润滑特性和在软骨表面的位置表明该分子具有软骨保护作用，有利于软骨的稳态。将来，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合理的框架。