Tammy Haut Donahue

Mechanotransduction in the Meniscus

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