Superficial Zone Protein (SZP) and Arthritis

浅层区蛋白 (SZP) 和关节炎

基本信息

批准号：
7596057
负责人：
THOMAS M SCHMID
金额：
$ 2.3万
依托单位：
RUSH UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-08-01 至 2010-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7596057
关键词：
Adhesives Affinity Age Anabolism Antibodies Arthritis Binding Biochemical Cartilage Cell Adhesion Cell Adhesion Molecules Cell-Matrix Junction Cells Charge Chondrocytes Code Complex Cultured Cells Data Depth Disease Enzyme-Linked Immunosorbent Assay Fostering Future Genes Glycoproteins Heparin Homeostasis Human Individual Integrins Joints Laboratories Liquid substance Location Lubricants Lubrication Measures Methods Monoclonal Antibodies Movement Mucinous Mucins Operative Surgical Procedures Organ Donor Osteoarthrosis Deformans Patients Production Property Protein Binding Protein Biosynthesis Protein Isoforms Proteins RNA Splicing Replacement Arthroplasty Serum Sialic Acids Surface Synovial Cell Synovial Fluid Tertiary Protein Structure Testing Tissue Harvesting Tissues Variant Vitronectin articular cartilage bone cytokine improved long bone lubricin macromolecule research study

项目摘要

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.

关节软骨是长骨头末端的一种血管，动脉和异质组织。它）至少两个功能。首先，它为两个运动提供了几乎无摩擦的表面阐明骨头。其次，它将负载从软骨表面传递到软骨下骨。能力执行这两个功能都取决于关节软骨表面的完整性及其能力抵抗磨损，因为两个相对的表面相互作用。一种称为浅层区的糖蛋白蛋白质（SZP）已从软骨组织纯化。 SZP特异的抗体表明分子为仅限于关节软骨的表面层，而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，这是主要的滑液中润滑糖蛋白。 SZP/润滑剂的边界润滑剂功能可能涉及 SZP与软骨表面的其他大分子的结合，因此SZP的结合特性将被调查。 SZP对玻霉素的同源性表明SZP可能具有细胞粘合剂特性，因此将研究SZP增强或抑制细胞粘附的能力。单克隆面板抗体将在三明治ELISA中使用，以测量滑液中SZP的浓度。滑膜将测试来自OA患者和器官供体的流体，以确定这些流体中SZP的浓度是否与这些人的软骨损伤程度相关。软骨细胞的能力将关节炎软骨与培养中的SZP合成的软骨与软骨细胞的合成能力进行比较来自捐助软骨。 SZP在软骨表面的润滑特性和位置表明分子是软骨保护性的，对软骨的稳态有益。将来这些研究应该有助于提供一个合理的框架，以改善数百万美元的关节润滑和运动患有关节炎的人。