Core B serves the overall function of procuring, processing and distributing human knee tissue and tissue extracts to the 3 research projects. The use of human tissues is a central and unifying part of the proposed experimental approach. Access to sufficient numbers of samples has been successfully maintained since the origin of this program. In the past cycle. Core B refined and standardized sample processing and analysis provided all projects with tissues, cells, and molecular extracts as needed. This service is a key feature and basis of this program. Core B also assumed an ancillary function to generate data for descriptive studies that will support hypothesis driven research. Core B will document the relevant parameters in articular cartilage and other joint tissues providing a multidisciplinary analysis of age-related changes in the knee. All projects can now study the same knee samples across the entire adult age spectrum. In addition to specific themes that are addressed by the 3 projects, the multidisciplinary analysis of the same human samples represents one of the central common approaches in the program.
The Specific Aims are to procure human knee joints (100 donors, 200 joints per year) from tissue banks;conduct macroscopic assessment;han/est specimens; perform microscopic assessment including semiquantitative and quantitative histology and histomorphometric measurements;isolate cells (chondrocytes, meniscal synovial, ligament cells);extract RNA, DNA, and protein;perform biomechanical testing;identify patterns of degeneration and determine relationships of changes in all joint tissues. In addition. Core B will store and distribute materials (tissue sections, DNA, RNA, proteins) nationally to other investigators. A major strength of this core is the analysis of the same tissue specimens in multiple experiments with different techniques to test different hypotheses This approach supports direct associations among the different observations and enhances the power of the observations. By performing a standardized evaluation of cartilage, and of all other joint tissues, changes that occur with aging can be identified and the relationship of changes in the different tissues can be determined. Comparison with similar specimens exhibiting OA presents a unique opportunity to define similarities and differences between the process of OA and that of aging. The studies proposed in all research components depend on these samples, and this core is thus essential to the success of the program.

Public Health Relevance

The objective of this program is to identify eariy mechanisms that lead to OA. The multimodal analysis of the entire knee is a unique opportunity to understand the process of OA and the difference from natural aging. This will lead to improved diagnostic and prognostic markers of OA and novel prophylactic and therapeutic approaches. Core B will process and store tissue sections and extracts to be distributed nationally to investigators which, when combined with the database of macroscopic, microscopic, and biomechanical measurements maintained by the core, will be a valuable contribution to the scientific community.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Program Projects (P01)
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Special Emphasis Panel (ZAG1-ZIJ-9 (04))
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Scripps Research Institute
La Jolla
United States
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