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Altered mechanical loading
of meniscal tissue occurs following various injuries and surgical
treatments such as anterior cruciate ligament (ACL) transection
and meniscectomy. The degenerative sequel of the joint following
both ACL transection and partial meniscectomy is well documented.
However, most studies have focused on the degradation of the articular
cartilage of the joint. Few studies have focused on how the meniscal
tissue responds to the altered loading. Other musculoskeletal tissues,
such as cartilage and bone, have been shown to respond to altered
loading with a biochemical response that in turn mediates tissue
remodeling. The biochemical events resulting from altered loading
of meniscal tissue have not been previously studied. Previous experimental
data by others, suggests that both interleukin-1 (IL-1) and nitric
oxide (NO) are important mediators in the degradation of musculoskeletal
tissues such as articular cartilage and meniscus. Furthermore, NO
has been shown to be upregulated in meniscal tissue following mechanical
compression. Therefore, the first hypothesis of this study is that
altered mechanical loading of meniscal tissue stimulates meniscal
cells to produce IL- 1 and NO in a magnitude dependent fashion.
The menisci are comprised of two geometrically distinct cell
populations; elliptical fibroblast-like cells in the superficial
zone, and spherical chondrocytic-like cells in the deep zone.
Following mechanical stimulation, only cells from the superficial
zone showed an increase in NO levels. In contrast, cells from the
deep zone were shown to produce NO following chemical stimulation,
but no increase in NO was seen following mechanical stimulation.
Therefore, the second hypothesis of this study is that elliptical
shaped cells elicit a greater biochemical response when subjected
to mechanical loading compared to spherical shaped meniscal cells.
To test these hypotheses, a custom mechanical testing system
will be built to compress meniscal explants to precise stresses
and strains after which the biochemical response will be measured.
Finite element modeling will be used determine the distinct mechanical
environment of both elliptical and spherical shaped cells, and the
cellular mechanical environment will be correlated to the biochemical
response.
Completion of this project
will provide a better understanding of the role of mechanical stimulation
in the physiology and pathophysiology of the meniscus. Joint degeneration
is the first step in the etiology of osteoarthritis. Improved treatment
following meniscal excision will depend on an understanding of mechanotransduction
in meniscal tissue. The findings of the current proposal will have
significant implications in the development of pharmaceutical and
biophysical interventions for the treatment of the degenerative
joint disease osteoarthritis.
Sponsored by The
Whitaker Foundation 8/03 - 8/06
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