Altered trabecular bone structure and delayed cartilage degeneration in the knees of collagen VI null mice.
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2012
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Mutation or loss of collagen VI has been linked to a variety of musculoskeletal abnormalities, particularly muscular dystrophies, tissue ossification and/or fibrosis, and hip osteoarthritis. However, the role of collagen VI in bone and cartilage structure and function in the knee is unknown. In this study, we examined the role of collagen VI in the morphology and physical properties of bone and cartilage in the knee joint of Col6a1(-/-) mice by micro-computed tomography (microCT), histology, atomic force microscopy (AFM), and scanning microphotolysis (SCAMP). Col6a1(-/-) mice showed significant differences in trabecular bone structure, with lower bone volume, connectivity density, trabecular number, and trabecular thickness but higher structure model index and trabecular separation compared to Col6a1(+/+) mice. Subchondral bone thickness and mineral content increased significantly with age in Col6a1(+/+) mice, but not in Col6a1(-/-) mice. Col6a1(-/-) mice had lower cartilage degradation scores, but developed early, severe osteophytes compared to Col6a1(+/+) mice. In both groups, cartilage roughness increased with age, but neither the frictional coefficient nor compressive modulus of the cartilage changed with age or genotype, as measured by AFM. Cartilage diffusivity, measured via SCAMP, varied minimally with age or genotype. The absence of type VI collagen has profound effects on knee joint structure and morphometry, yet minimal influences on the physical properties of the cartilage. Together with previous studies showing accelerated hip osteoarthritis in Col6a1(-/-) mice, these findings suggest different roles for collagen VI at different sites in the body, consistent with clinical data.
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Christensen, Susan E, Jeffrey M Coles, Nicole A Zelenski, Bridgette D Furman, Holly A Leddy, Stefan Zauscher, Paolo Bonaldo, Farshid Guilak, et al. (2012). Altered trabecular bone structure and delayed cartilage degeneration in the knees of collagen VI null mice. PLoS One, 7(3). p. e33397. 10.1371/journal.pone.0033397 Retrieved from https://hdl.handle.net/10161/15320.
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Scholars@Duke
Holly Leddy
Holly A. Leddy, PhD
Holly Leddy holds a PhD in biomedical engineering from Duke University and an BA in biology from Bowdoin College. She is currently a Research and Development engineer at the Shared Materials and Instrumentation Facility (SMIF) at Duke University. She leads both the Outreach and the Characterization teams. She has expertise in many types of microscopy and worked for many years in the field of cartilage mechanobiology. She has also created a vibrant outreach program at SMIF that brings the excitement of nanoscale science to thousands of people annually through both virtual and hands-on experiences.
Stefan Zauscher
My research lies at the intersection of surface and colloid science, polymer materials engineering, and biointerface science, with four central areas of focus:
- Fabrication, manipulation and characterization of stimulus-responsive biomolecular and bio-inspired polymeric nanostructures on surfaces;
- Nanotechnology of soft-wet materials and hybrid biological/non-biological microdevices;
- Receptor-ligand interactions relevant to the diagnostics of infectious diseases;
- Friction of soft-wet materials, specifically the role of glycoproteins on friction in diarthroidal joints.
These four broad lines of inquiry deal with fundamental behaviors of soft-wet materials on surfaces and interfaces. The design and fabrication of these interfaces using "smart" polymeric and biomolecular nanostructures, and the characterization of the resulting structures, are critically important for the development of biomolecular sensors and devices and for bioinspired materials. Key approaches and tools I use in my research are: bottom-up organization on the molecular scale, through self-assembly, in-situ polymerization, and manipulation of intermolecular interactions; topdown fabrication, through scanning probe nanolithography; stimulus-responsive polymers; molecular recognition; and new approaches to sensing and manipulation. This research supports Duke's Pratt School of Engineering strategic initiative to expand research in soft-wet Materials Science.
Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.