Cyclic mechanical stretching modulates secretion pattern of growth factors in human tendon fibroblasts

Abstract

The objective of the study was to investigate whether the response profile of the growth factor of human tendon fibroblasts could be beneficially influenced through the application of mechanical stretch. It was considered that this would elucidate structural and functional problems, often seen after tendon and ligament healing. The secretion pattern of transforming growth factor-beta (TGF-beta), platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) was determined in mechanically stretched fibroblasts and compared to non-stretched controls. Human tendon fibroblasts were experimentally stretched for 15 and 60 mm at a frequency of 1 Hz and an amplitude of 5%. The secretion of TGF-beta PDGF and bFGF was measured by enzyme-linked immuno-sorbent assay. All the growth factors investigated were indeed secreted by human tendon fibroblasts both in stretched cells and controls. Mechanical stretch increased the secretion pattern of the growth factors. The increased concentrations of TGF-beta bFGF and PDGF after cyclical mechanical stretching may have a positive influence on tendon and ligament healing through stimulation of cell proliferation, differentiation and matrix formation.

Cyclic strain influences the expression of the vascular endothelial growth factor (VEGF) and the hypoxia inducible factor 1 alpha (HIF‐1α) in tendon fibroblasts

“…The responsiveness of connective tissue cells such as osteoblasts, chondrocytes and fibroblasts to mechanical strain has been confirmed by several in vitro investigations and the effect of cyclic strain on tendon cells has been associated with a diverse array of biological responses [ 1- 3,6,5,12,19,24,30,38,46,47,49,53,54]. These cellular features are necessary to restore the normal mechanical properties of the tissue after injury or during a remodeling process (e.g.…”

“…We used a silicon well with dimensions as first stated by Zeichen et al [54]. Since this group studied the effect of mechanical strain on the expression of various proteins in tendon cells [12,46,47,49,50,52] we used the same model to study the effect of mechanical strain on VEGF expression.…”

“…The dishes were optically clear and had a cell culture surface area of 50 mm x 23 mm. This model has been used in previous studies [12,46,47,49,54]. The dishes were molded of a two component silicone elastomer containing Silicosehl RTV 270 and crosslinker A 47 (Rhone Poulenc, Liibeck, Germany).…”

The Role of Mechanical Loading in Tendon Development, Maintenance, Injury, and Repair

“…These experiments support the beneficial effect of mechanical load and the need for its incorporation in both clinical postoperative rehabilitation protocols and in tissue-engineering applications 27 . It is hypothesized that the cell population of a tendon responds to the application of mechanical stress and modulation of the extracellular matrix through the activation and/or effects of a number of growth factors, including transforming growth factor-b1 (TGF-b1), connective tissue growth factor, and interleuken-6 (IL-6) [28][29][30] . Type-I collagen synthesis and deposition have been linked to increasing expression levels of TGF-b1 both in human Achilles tendon studies and studies investigating the effects of cyclic loading on TGF-b1 expression in human tendon fibroblasts 29,30 .…”

Extracorporeal shock waves promote healing of collagenase‐induced Achilles tendinitis and increase TGF‐β1 and IGF‐I expression

“…Tenocytes have been found to convert biophysical stimulation into a biochemical response leading to release of growth factors and cellular adaptation [29]. Of the growth factors regulating tendon repair, TGF-p and insulin-like growth factor-I (IGF-I) have been found to promote tendon regeneration by regulating collagen metabolism and tenocyte proliferation [1, 2,5,25].…”