Tendinopathies induced by overuse during occupational or athletic activity are a musculoskeletal problem of growing magnitude. The lack of effective models for studying tendinopathy has hampered efforts to understand the underlying mechanism of these disorders and to evaluate the effectiveness of therapies to treat these disorders. In this study cyclical loading regimens of variable magnitude and duration will be applied to tendon explants in tissue culture as a novel means to investigate injury mechanism and treatment issues related to overuse tendinopathy. The overall objective of this study is to characterize the tissue response occurring with cyclical loading in our accelerated overuse injury model and utilize the model to evaluate therapies for treating tendon injuries.
The specific aims of the study are: 1. To evaluate the injury-response of tendon explants to cyclical loading regimens of variable amplitude (3, 6, 12, 24, 36 MPa Peak) and duration (1day-24hr daily, 3day-8hr daily, 6day-4hr daily). Tissue injury will be evaluated by PGE2 release to the medium, cell viability, matrix metalloproteinase activity (MMP) of the medium, tissue collagen content, tissue proteoglycan content, collagen Iii content, biomechanical properties and tissue organization by analysis of hemotoxlyin and eosin stained sections. 2. To evaluate the influence of specific cyclooygenase (COX-1/2) inhibitors (1 :SC-560, 2: Celecoxib) in modulating the tissue response (as measured in aim 1) of tendon explants to the cyclical loading regimens of aim1. 3. To evaluate the influence of the magnitude ( no load-control, low-load: 3MPa, moderate-load: 6MPa) of postinjury cyclical loading (1hour daily at 0.5Hz ) on the recovery to preinjury tissue characteristics (as measured in aim 1) at 1 and 2 weeks postinjury. The initial injury will be produced utilizing the cyclical loading regimen of aim 1 that has been demonstrated to best mimic the tissue changes observed in clinical overuse tendinopathy. These studies will characterize a new model for studying issues related to overuse tendinopathy, elucidate the role of COX in the injury mechanism of overuse tendinopathy, and assess if low-load exercises are of equal benefit as moderate-load exercises for promoting tissue recovery after injury.
| Devkota, Aaditya C; Weinhold, Paul S (2010) Prostaglandin E(2), collagenase, and cell death responses depend on cyclical load magnitude in an explant model of tendinopathy. Connect Tissue Res 51:306-13 |
