EXCEED THE SPACE PROVIDED. The mechanical environment of the chondrocytes is an important factor that affects the health and function of the diarthrodial joint. The mechanical signals to which chondrocytes are exposed depend on the biomechanical interactions between the cell, pericellular matrix, and extracellular matrix. Currently, there is little or no information available on the mechanical properties of the pericellular matrix of articular cartilage. The goals of this study are to measure the intrinsic biomechanical and diffusion properties of the chondrocyte pericellular matrix, and to test the hypothesis that these properties are altered in osteoarthritic cartilage. Furthermore, we propose that type VI collagen, which is abundantly present in the pericellular matrix, influences the physical properties of this region. We will use several novel experimental techniques to quantify the micromechanical behavior of pericellular matrix using the isolated _hondron model.
The specific aims of this study are: 1) Measure the mechanical properties of the 3ericellular matrix from normal and osteoarthritic cartilage using micropipette aspiration and atomic force microscopy, incorporate these findings in a theoretical model of cell-matrix interactions in cartilage, and validate these predictions using 3D confocal microscopy; 2) Measure the diffusion properties of the pericellular matrix of normal and OA cartilage; 3) Determine how the presence of a normal or OA pericellular matrix influences the metabolic response of chondrocytes to dynamic compression within an lartificial matrix; and 4) Determine what role type VI collagen plays in the mechanical properties of the pericellular matrix. The long-term goals of this study are to improve our understanding of the role of mechanical factors in the regulation of cartilage metabolism in normal and diseased conditions. A better understanding of these pathways will hopefully lead to the development of new pharmaceutical or biophysical interventions for the treatment of osteoarthritis. PERFORMANCE SITE ========================================Section End===========================================

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG015768-08
Application #
6841641
Study Section
Orthopedics and Musculoskeletal Study Section (ORTH)
Program Officer
Kohanski, Ronald A
Project Start
1998-01-01
Project End
2007-12-31
Budget Start
2005-01-01
Budget End
2005-12-31
Support Year
8
Fiscal Year
2005
Total Cost
$346,500
Indirect Cost
Name
Duke University
Department
Surgery
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Guilak, Farshid; Nims, Robert J; Dicks, Amanda et al. (2018) Osteoarthritis as a disease of the cartilage pericellular matrix. Matrix Biol 71-72:40-50
Rowland, Christopher R; Glass, Katherine A; Ettyreddy, Adarsh R et al. (2018) Regulation of decellularized tissue remodeling via scaffold-mediated lentiviral delivery in anatomically-shaped osteochondral constructs. Biomaterials 177:161-175
Furman, Bridgette D; Kent, Collin L; Huebner, Janet L et al. (2018) CXCL10 is upregulated in synovium and cartilage following articular fracture. J Orthop Res 36:1220-1227
Tang, Ruhang; Jing, Liufang; Willard, Vincent P et al. (2018) Differentiation of human induced pluripotent stem cells into nucleus pulposus-like cells. Stem Cell Res Ther 9:61
Erdemir, Ahmet; Hunter, Peter J; Holzapfel, Gerhard A et al. (2018) Perspectives on Sharing Models and Related Resources in Computational Biomechanics Research. J Biomech Eng 140:
Adkar, Shaunak S; Brunger, Jonathan M; Willard, Vincent P et al. (2017) Genome Engineering for Personalized Arthritis Therapeutics. Trends Mol Med 23:917-931
Liu, Betty; Goode, Adam P; Carter, Teralyn E et al. (2017) Matrix metalloproteinase activity and prostaglandin E2 are elevated in the synovial fluid of meniscus tear patients. Connect Tissue Res 58:305-316
Wu, Chia-Lung; Kimmerling, Kelly A; Little, Dianne et al. (2017) Serum and synovial fluid lipidomic profiles predict obesity-associated osteoarthritis, synovitis, and wound repair. Sci Rep 7:44315
Brunger, Jonathan M; Zutshi, Ananya; Willard, Vincent P et al. (2017) CRISPR/Cas9 Editing of Murine Induced Pluripotent Stem Cells for Engineering Inflammation-Resistant Tissues. Arthritis Rheumatol 69:1111-1121
Wu, Chia-Lung; McNeill, Jenna; Goon, Kelsey et al. (2017) Conditional Macrophage Depletion Increases Inflammation and Does Not Inhibit the Development of Osteoarthritis in Obese Macrophage Fas-Induced Apoptosis-Transgenic Mice. Arthritis Rheumatol 69:1772-1783

Showing the most recent 10 out of 229 publications