Articular cartilage is the connective tissue that lines joints and provides a
smooth surface for articulation and shock absorption. Osteoarthritis, the
progressive degeneration of cartilage, is a painful, debilitating, and widespread
disease, affecting 70% of people over 65. Because cartilage is avascular,
molecular transport occurs primarily via diffusion. The goal of these studies was
to examine whether cartilage matrix structure and composition have a significant
effect on diffusive transport.
We hypothesized that diffusion is anisotropic in the surface zone of
cartilage where collagen structure is aligned and densely packed. A theoretical
model and experimental protocol for fluorescence imaging of continuous point
photobleaching (FICOPP) were developed to measure diffusional anisotropy.
Significant anisotropy was observed in ligament, a highly ordered collagenous
tissue. In less ordered articular cartilage, diffusional anisotropy was dependent
on site in the tissue and size of the diffusing molecule. These findings suggest
that diffusional transport of macromolecules is anisotropic in collagenous tissues,
with higher rates of diffusion along primary orientation of collagen fibers.
We hypothesized that structural differences in the pericellular matrix of
cartilage (PCM) would lead to differences in diffusive properties as compared to
the surrounding extracellular matrix (ECM). We modified the scanning
microphotolysis (SCAMP) technique to allow measurement of diffusion
coefficients within the PCM. Diffusion coefficients in the PCM were lower than
in the adjacent ECM in normal cartilage, but with early stage arthritis, the PCM
diffusivity was not different from that of the ECM. These data suggest that
breakdown of the PCM is an early step in arthritis development.
We hypothesized that compression of cartilage would cause site‐specific
diffusivity decreases and diffusional anisotropy increases. We utilized SCAMP
and FICOPP to measure diffusion coefficients and diffusional anisotropy in
cartilage as it was compressed. We found that diffusivity decreased and
anisotropy increased with increasing strain in a site‐specific manner. These
findings suggest that the high surface zone strains that lead to low diffusivity
and high anisotropy will decrease transport between cartilage and synovial fluid
in compressed cartilage. We have shown that matrix structure and composition
have a significant effect on diffusive transport in cartilage. / Dissertation
| Identifer | oai:union.ndltd.org:DUKE/oai:dukespace.lib.duke.edu:10161/170 |
| Date | 14 March 2007 |
| Creators | Leddy, Holly Anne |
| Contributors | Guilak, Farhid, Jacobson, Kenneth Alan, Lubkin, Sharon R., Setton, Lori A., Truskey, George A. |
| Source Sets | Duke University |
| Language | en_US |
| Detected Language | English |
| Type | dissertation |
| Format | 16732305 bytes, application/pdf |
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