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Tendon degeneration due to repetitive loading: An in vivo tendinopathy model

Posted on:2007-07-22Degree:Ph.DType:Dissertation
University:University of California, San Francisco with the University of California, BerkeleyCandidate:Nakama, Leena HFull Text:PDF
GTID:1454390005990950Subject:Biomedical engineering
Abstract/Summary:
The goals of this dissertation were to investigate the effects of different loading patterns on tendon degeneration. An in vivo rabbit model was developed to expose the tendon to repetitive loading for 2 hours per day, 3 days per week for 12 weeks (80 cumulative hours). Three combinations of peak forces (High: 0.42N; Low: 0.14N) and repetition rates (High: 60 reps/min; Low: 10 reps/min) were selected: High Force/High Repetition (HFHR), High Force/Low Repetition (HFLR) and Low Force/High Repetition (LFHR). At the end of the exposure period, changes to tendon microstructure and biology were measured.;Microtears were quantified using photomicroscopy and image analysis methods. Biological changes were measured by immunohistochemical staining of cells for growth factors associated with angiogenesis and matrix repair (VEGF, VEGFR-1 and CTGF).;Microtears were increased under HFHR loading. There were moderate increases with HFLR loading and no changes associated with LFHR loading. Dose-response relationships were observed for both force and repetition with tear measures being affected more by peak force than repetition rate.;Cell densities of VEGF, VEGFR-1 and CTGF staining cells were increased under HFHR loading. No changes were found under the other loading conditions. VEGF staining cell density correlated to microtears (tear density) regardless of the loading pattern. VEGFR-1 cell density, the main receptor for VEGF, was associated to tear density only under HFHR loading.;The results presented here may provide a better understanding of the underlying mechanisms that occur between the cellular and microstructural responses of the tendon undergoing repetitive loading leading to the degeneration. As the tendon experiences repetitive loading, microtears may accumulate causing a cellular response, such as an upregulation of VEGFR-1. This may provide a pathway for inflammatory and angiogenic mediators further downstream in tendon degeneration.;These results may be applied to the workplace and suggest a strategy for preventing or managing tendon-related injuries among workers. In translation, the findings suggest that in order to decrease risk of tendon related injuries among workers due to hand intensive tasks, greater benefit may be obtained by reducing the peak hand loads than by reducing repetition rates.
Keywords/Search Tags:Loading, Tendon, Repetition, VEGF
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