An in vitro investigation into the effects of 10 Hz cyclic loading on tenocyte metabolism

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 8‐12 Hz. 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 10 Hz perturbations on tenocyte metabolism, comparing gene expression in response to a 10 Hz and 1 Hz loading profile. Tenocytes from healthy and tendinopathic human tendons were seeded into 3D collagen gels and subjected to 15 minutes cyclic strain at 10 Hz or 1 Hz. 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 10 Hz, relative to 1 Hz loading. By contrast, whilst the response of tenocytes from tendinopathy tendon also increased with 10 Hz 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 10 Hz 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.

Multimodal analysis of the differential effects of cyclic strain on collagen isoform composition, fibril architecture and biomechanics of tissue engineered tendon

“…Herein COL2A1 expression was the lowest of all genes evaluated by qPCR, indicating that even non-dynamic tensile forces (control group) inhibit COL2A1 transcription, consistent with previously reported absent expression of COL2A1 from tenocytes given 24 h of cyclic 1% strain at 10 Hz or in tendon fascicles. 35,36 For COL1 and COL3A1, a previous study in comparable fibrin hydrogels found that porcine MSCs subjected to 7 days of 10% cyclic tensile strain at 0.5 Hz increased COL1A1 but decreased COL3A1 expression. 12 In other scaffolds alterations in COL1 and COL3A1 gene expression have been reported.…”

Growth factor and macromolecular crowding supplementation in human tenocyte culture

“…To this end, various biophysical (e.g. surface topography [ 22 , 23 ], mechanical stimulation [24] ), biochemical (e.g. physiological low oxygen tension [25] , media supplements [26] ), biological (e.g.…”

A Self‐Powered Piezo‐Bioelectric Device Regulates Tendon Repair‐Associated Signaling Pathways through Modulation of Mechanosensitive Ion Channels

“…[34] Under physiological conditions, the strain rate of the tendon is around 0.1-0.5 Hz; however, during intense activity, the frequency can be as high as 10 Hz. [35,36] Recently, it has been demonstrated that tendon cells modulate their gene expression, protein synthesis and mitogenesis in vitro through activation of mechanotransductive signaling pathways under physiological mechanical stimulation. [37] Therefore, we compared the effect of mechanical and electromechanical stimulation on human hTDCs gene and protein expression (Table 3, 4 and 5) (Figure 5).…”