INDUCTION OF TISSUE TRANSGLUTAMINASE BY DYNAMIC LOAD

通过动态负载诱导组织转谷氨酰胺酶

• 批准号: 6622702
• 负责人: RONALD DAVID GRAFF
• 金额: $ 5.63万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-10-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6622702
• 关键词: chondrocytes; crosslink; enzyme induction /repression; extracellular matrix proteins; immunocytochemistry; in situ hybridization; mechanical pressure; molecular film; polymerase chain reaction; protein glutamine gamma glutamyltransferase; tissue /cell culture

The objective of this proposal is to further our understanding of the mechanisms by which chondrocytes respond to dynamic mechanical load. Tissue transglutaminase (tTG) stabilizes extracellular matrix of many tissues, including cartilage, via the cross-linking of proteins such as fibronectin and collagen and may be important for the strengthening or remodeling of cartilage matrix in response to dynamic load. Furthermore, disruption of normal tTG functioning may contribute to the development or progression of osteoarthritis. The aims of this proposal are: l) to examine by immunocytochemistry and in situ hybridization the expression and localization of tTG in chondron pellet cultures before and after cyclic compressive loading; 2) to measure the cross-linking activity of tTG in response to cyclic compressive loading in chondron pellet cultures by examining the incorporation of exogenous tTG substrates; 3) to identify immunologically the endogenous matrix proteins which are cross-linked by tTG in loaded chondron pellets, and determine the pattern of cross-linking induced by loads of different strengths. These studies will provide a clearer understanding of the role of tTG in articular cartilage.

该提案的目的是进一步了解软骨细胞对动态机械负载反应的机制。组织转谷氨酰胺酶（TTG）通过蛋白质（例如纤连蛋白和胶原蛋白）的交联，包括软骨在内的许多组织（包括软骨）的细胞外基质稳定，对动态负载的响应而对软骨基质的增强或重塑可能很重要。此外，正常TTG功能的破坏可能有助于骨关节炎的发展或发展。该提案的目的是：l）通过免疫细胞化学和原位杂交检查循环压缩载荷之前和之后，TTG在软骨颗粒培养物中的表达和定位； 2）通过检查外源性TTG底物的掺入，测量TTG对循环压缩载荷的交联活性； 3）在免疫学上鉴定内源性基质蛋白，这些基质蛋白在加载的软骨颗粒中与TTG交联，并确定由不同强度的负载引起的交联模式。这些研究将对TTG在关节软骨中的作用有更清晰的了解。