Abstract

Tendinopathy is a prevalent, highly debilitating condition, with poorly defined etiology. A wide range of clinical treatments has been proposed, with systematic reviews largely supporting shock wave therapy or eccentric exercise. Characterizing these treatments have demonstrated both generate perturbations within tendon at a frequency of approximately 8-12Hz. Consequently, it is hypothesized that loading in this frequency range initiates increased anabolic tenocyte behavior, promoting tendon repair. The primary aim of this study was to investigate the effects of 10Hz perturbations on tenocyte metabolism, comparing gene expression in response to a 10Hz and 1Hz loading profile. Tenocytes from healthy and tendinopathic human tendons were seeded into 3D collagen gels and subjected to 15minutes cyclic strain at 10Hz or 1Hz. Tenocytes from healthy tendon showed increased expression of all analyzed genes in response to loading, with significantly increased expression of inflammatory and degradative genes with 10Hz, relative to 1Hz loading. By contrast, whilst the response of tenocytes from tendinopathy tendon also increased with 10Hz loading, the overall response profile was more varied and less intense, possibly indicative of an altered healing response. Through inhibition of the pathway, IL1 was shown to be involved in the degradative and catabolic response of cells to high-frequency loading, abrogating the loading response. This study has demonstrated for the first time that loading at a frequency of 10Hz may enhance the metabolic response of tenocytes by initiating an immediate degradatory and inflammatory cell response through the IL1 pathway, perhaps as an initial stage of tendon healing.

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