The mechanical environment of the chondrocytes is an important factor that affects the health and function of the diarthrodial joint. The biomechanical and physicochemical signals to which chondrocytes are exposed depend on the interactions between the cell, pericellular matrix, and extracellular matrix of articular cartilage. The goals of this study are to measure the intrinsic biomechanical, physicochemical, 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 in combination with theoretical modeling to quantify the triphasic mechanical properties of the pericellular matrix in the isolated chondron model and in transgenic mice.
The specific aims of this study are: 1) Measure the mechanical properties of the pericellular matrix from normal and osteoarthritic cartilage using micropipette aspiration and atomic force microscopy, incorporate these findings in a theoretical multiphasic model of cell-matrix interactions in cartilage, and validate these predictions using confocal microscopy;2) Measure the diffusion properties of the pericellular matrix of normal and OA cartilage;3) Determine the effect of deleting type VI collagen on these mechanical and physicochemical 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.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
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Skeletal Biology Structure and Regeneration Study Section (SBSR)
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Williams, John
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Duke University
Schools of Medicine
United States
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Rowland, Christopher R; Colucci, Lina A; Guilak, Farshid (2016) Fabrication of anatomically-shaped cartilage constructs using decellularized cartilage-derived matrix scaffolds. Biomaterials 91:57-72
Lozoya, Oswaldo A; Gilchrist, Christopher L; Guilak, Farshid (2016) Universally Conserved Relationships between Nuclear Shape and Cytoplasmic Mechanical Properties in Human Stem Cells. Sci Rep 6:23047
Moutos, Franklin T; Glass, Katherine A; Compton, Sarah A et al. (2016) Anatomically shaped tissue-engineered cartilage with tunable and inducible anticytokine delivery for biological joint resurfacing. Proc Natl Acad Sci U S A 113:E4513-22
Huebner, J L; Landerman, L R; Somers, T J et al. (2016) Exploratory secondary analyses of a cognitive-behavioral intervention for knee osteoarthritis demonstrate reduction in biomarkers of adipocyte inflammation. Osteoarthritis Cartilage 24:1528-34
Kanju, Patrick; Chen, Yong; Lee, Whasil et al. (2016) Small molecule dual-inhibitors of TRPV4 and TRPA1 for attenuation of inflammation and pain. Sci Rep 6:26894
O'Conor, Christopher J; Ramalingam, Sendhilnathan; Zelenski, Nicole A et al. (2016) Cartilage-Specific Knockout of the Mechanosensory Ion Channel TRPV4 Decreases Age-Related Osteoarthritis. Sci Rep 6:29053
Zelenski, Nicole A; Leddy, Holly A; Sanchez-Adams, Johannah et al. (2015) Type VI Collagen Regulates Pericellular Matrix Properties, Chondrocyte Swelling, and Mechanotransduction in Mouse Articular Cartilage. Arthritis Rheumatol 67:1286-94
McNulty, Amy L; Guilak, Farshid (2015) Mechanobiology of the meniscus. J Biomech 48:1469-78
Wu, Chia-Lung; Jain, Deeptee; McNeill, Jenna N et al. (2015) Dietary fatty acid content regulates wound repair and the pathogenesis of osteoarthritis following joint injury. Ann Rheum Dis 74:2076-83
McNulty, Amy L; Leddy, Holly A; Liedtke, Wolfgang et al. (2015) TRPV4 as a therapeutic target for joint diseases. Naunyn Schmiedebergs Arch Pharmacol 388:437-50

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