DUKE UNIVERSITY
SCHOOL OF MEDICINE
DUKEHEALTH.ORG
| Research |
| Overview | Cell Mechanobiology | Tissue Mechanobiology Joint Biomechanics | Tissue Engineering |
Tissue Mechanobiology
Tissue Studies
At the tissue levels, we seek to investigate the interplay between mechanical factors and biochemical factors (e.g., matrix molecules, genetic factors, or soluble mediators such as cytokines and growth factors) in the regulation of chondrocyte physiology in normal and disease states.
These studies include:
Local Molecular Diffusion in articular cartilage
Diffusive transport of solutes is critical to the normal function of articular cartilage. The diffusion of macromolecules through cartilage may be affected by the local composition and structure, which vary with depth from the tissue surface.
We utilize method of Fluorescence Recovery After Photobleacing (FRAP) to measure local molecular diffusion coefficients in articular cartilage. FRAP provides an effective way to measure site-specific diffusion in cartilage. We have shown that diffusion of large molecules in cartilage is size dependent, and that diffusion of these uncharged molecules in cartilage is also zone dependent, but the pattern varies with molecular size.
Molecular Diffusion Using FRAP
References:
- Leddy HA, Guilak F. (2003) Site-specific molecular diffusion in articular cartilage measured using fluorescence recovery after photobleaching. Annals of Biomedical Engineering, 31 (7): 753-760
Mechanical stress, inflammation, and metabolism in articular cartilage and the meniscus
With injury or arthritis, intra-articular tissues of the knee joint such as cartilage and the meniscus may be exposed to significant changes in its biochemical and biomechanical environments that likely contribute to the progression of joint disease. By examining the influence of mechanical stress on matrix turnover in these tissues in the presence of inflammatory mediators such as interleukin-1 (IL-1) we can begin to understand the mechanism of disease progression and better understand the role of nitric oxide (NO) in these processes. Explants of tissue are subjected to dynamic compressive stresses at various amplitudes and frequencies with multiple dosages of IL-1 and various drugs, cytokines, and antagonists. The synthesis of total protein, proteoglycan, and NO among other parameters are typically monitored. Our findings strongly suggest that IL-1 may modulate the effects of mechanical stress on extracellular matrix turnover through a pathway that is dependent on NO.
Mechanical Stress & Inflammation
References:
- Fermor, B., Weinberg, J.B., Pisetsky, D.S., Misukonis, M.A., Banes, A.J., and Guilak, F. (2001): The effects of static and dynamic compression on nitric oxide production in articular cartilage explants. Journal of Orthopaedic Research, 19(4):72-80.
- Fermor, B., Haribabu, B., Weinberg, J.B., Pisetsky, D.S., and Guilak, F. (2001):Mechanical stress and nitric oxide influence leukotriene production in cartilage, Biochemical and Biophysical Research Communications, 285(3):806-810.
- Fink, C., Fermor, B., Weinberg, J.B., Pisetsky, D.S., Misukonis, M.A., and Guilak, F. (2001): Dynamic mechanical compression increases nitric oxide production in the meniscus. Osteoarthritis & Cartilage, 9(5):481-487.
- LeGrand, A., Fermor, B., Fink, C., Pisetsky, D.S., Weinberg, J.B., Vail, T.P., and Guilak, F. (2001): IL 1, TNF-alpha, and IL-17 synergistically upregulate nitric oxide and prostaglandin E2 production in explants of human osteoarthritic knee menisci. Arthritis and Rheumatism, 44:2078-83.
- Fermor B. Weinberg JB. Pisetsky DS. Misukonis MA. Fink C. Guilak F. Induction of cyclooxygenase-2 by mechanical stress through a nitric oxide-regulated pathway. Osteoarthritis & Cartilage. 10(10):792-8, 2002 Oct.
- Shin SJ, Fermor B, Weinberg JB, Pisetsky DS, Guilak F. Regulation of matrix turnover in meniscal explants: role of mechanical stress, interleukin-1, and nitric oxide. Journal of Applied Physiology, 95 (1): 308-313 JUL 2003
Oxygen and inflammatory mediators in cartilage
Articular cartilage is an avascular tissue that functions at a lower oxygen tension than do most tissues. With mobilization, arthritic joints may undergo cycles of hypoxia (reduced oxygen) and reoxygenation. Data from our studies do indeed suggest that oxygen tension may influence inflammation associated with cartilage injury and disease.
Hypoxia and Inflammation
At the tissue levels, we seek to investigate the interplay between mechanical factors and biochemical factors (e.g., matrix molecules, genetic factors, or soluble mediators such as cytokines and growth factors) in the regulation of chondrocyte physiology in normal and disease states.
These studies include:
Local Molecular Diffusion in articular cartilage
Diffusive transport of solutes is critical to the normal function of articular cartilage. The diffusion of macromolecules through cartilage may be affected by the local composition and structure, which vary with depth from the tissue surface.
We utilize method of Fluorescence Recovery After Photobleacing (FRAP) to measure local molecular diffusion coefficients in articular cartilage. FRAP provides an effective way to measure site-specific diffusion in cartilage. We have shown that diffusion of large molecules in cartilage is size dependent, and that diffusion of these uncharged molecules in cartilage is also zone dependent, but the pattern varies with molecular size.
Molecular Diffusion Using FRAP
References:
- Leddy HA, Guilak F. (2003) Site-specific molecular diffusion in articular cartilage measured using fluorescence recovery after photobleaching. Annals of Biomedical Engineering, 31 (7): 753-760
Mechanical stress, inflammation, and metabolism in articular cartilage and the meniscus
With injury or arthritis, intra-articular tissues of the knee joint such as cartilage and the meniscus may be exposed to significant changes in its biochemical and biomechanical environments that likely contribute to the progression of joint disease. By examining the influence of mechanical stress on matrix turnover in these tissues in the presence of inflammatory mediators such as interleukin-1 (IL-1) we can begin to understand the mechanism of disease progression and better understand the role of nitric oxide (NO) in these processes. Explants of tissue are subjected to dynamic compressive stresses at various amplitudes and frequencies with multiple dosages of IL-1 and various drugs, cytokines, and antagonists. The synthesis of total protein, proteoglycan, and NO among other parameters are typically monitored. Our findings strongly suggest that IL-1 may modulate the effects of mechanical stress on extracellular matrix turnover through a pathway that is dependent on NO.
Mechanical Stress & Inflammation
References:
- Fermor, B., Weinberg, J.B., Pisetsky, D.S., Misukonis, M.A., Banes, A.J., and Guilak, F. (2001): The effects of static and dynamic compression on nitric oxide production in articular cartilage explants. Journal of Orthopaedic Research, 19(4):72-80.
- Fermor, B., Haribabu, B., Weinberg, J.B., Pisetsky, D.S., and Guilak, F. (2001):Mechanical stress and nitric oxide influence leukotriene production in cartilage, Biochemical and Biophysical Research Communications, 285(3):806-810.
- Fink, C., Fermor, B., Weinberg, J.B., Pisetsky, D.S., Misukonis, M.A., and Guilak, F. (2001): Dynamic mechanical compression increases nitric oxide production in the meniscus. Osteoarthritis & Cartilage, 9(5):481-487.
- LeGrand, A., Fermor, B., Fink, C., Pisetsky, D.S., Weinberg, J.B., Vail, T.P., and Guilak, F. (2001): IL 1, TNF-alpha, and IL-17 synergistically upregulate nitric oxide and prostaglandin E2 production in explants of human osteoarthritic knee menisci. Arthritis and Rheumatism, 44:2078-83.
- Fermor B. Weinberg JB. Pisetsky DS. Misukonis MA. Fink C. Guilak F. Induction of cyclooxygenase-2 by mechanical stress through a nitric oxide-regulated pathway. Osteoarthritis & Cartilage. 10(10):792-8, 2002 Oct.
- Shin SJ, Fermor B, Weinberg JB, Pisetsky DS, Guilak F. Regulation of matrix turnover in meniscal explants: role of mechanical stress, interleukin-1, and nitric oxide. Journal of Applied Physiology, 95 (1): 308-313 JUL 2003
Oxygen and inflammatory mediators in cartilage
Articular cartilage is an avascular tissue that functions at a lower oxygen tension than do most tissues. With mobilization, arthritic joints may undergo cycles of hypoxia (reduced oxygen) and reoxygenation. Data from our studies do indeed suggest that oxygen tension may influence inflammation associated with cartilage injury and disease.
Hypoxia and Inflammation
References:
- Cernanec J. Guilak F. Weinberg JB. Pisetsky DS. Fermor B. Influence of hypoxia and reoxygenation on cytokine-induced production of proinflammatory mediators in articular cartilage. Arthritis & Rheumatism. 46(4):968-75, 2002 Apr.
Above links open in new windows
DHTS WEB SERVICES