Rabbit tendon cells produce MMP-3 in response to fluid flow without significant calcium transients

Faculty of Kinesiology, Human Performance Laboratory, University of Calgary, 2500 University Drive, NW Calgary, Alberta, Canada T2N 1N4.
Journal of Biomechanics (Impact Factor: 2.75). 04/2002; 35(3):303-9. DOI: 10.1016/S0021-9290(01)00217-2
Source: PubMed

ABSTRACT Forces applied to tendon during movement cause cellular deformation, as well as fluid movement. The goal of this study was to test the hypothesis that rabbit tendon fibroblasts detect and respond to fluid-induced shear stress. Cells were isolated from the paratenon of the rabbit Achilles tendon and then subjected to fluid flow at 1 dyn/cm(2) for 6h in a specially designed multi-slide flow device. The application of fluid flow led to an increased expression of the collagenase-1 (MMP-1), stromelysin-1 (MMP-3), cyclooxygenase II (COX-2) and interleukin-1beta (IL-1beta) genes. The release of proMMP-3 into the medium exhibited a dose-response with the level of fluid shear stress. However, not all cells aligned in the direction of flow. In other experiments, the same cells were incubated with the calcium-reactive dye FURA-2 AM, then subjected to laminar fluid flow in a parallel plate flow chamber. The cells did not significantly increase intracellular calcium concentration when exposed to fluid shear stress levels of up to 25 dyn/cm(2). These results show that gene expression in rabbit tendon cells is sensitive to fluid flow, but that signal transduction is not dependent on intracellular calcium transients. The upregulation of the MMP-1, MMP-3 and COX-2 genes shows that fluid flow could be an important mechanical stimulus for tendon remodelling or injury.

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Available from: Albert J Banes, Sep 26, 2015
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    • "This population proliferates and increases overall synthesis of extracellular matrix proteins in tendon in response to exercise (Zhang et al. 2010). Tendon cells' in vitro responses to mechanical stimuli have been studied using silicone substrates applying simultaneous substrate deformation and fluid flow (Thompson et al. 2011), with low strain magnitude effects promoting anabolic activity, that is secretion of extracellular matrix proteins, and higher magnitudes more catabolic, that is, secretion of enzymes responsible for breaking down extracellular matrix proteins (Yang and Im 2005; Archambault et al. 2002; Yang et al. 2004). "
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    ABSTRACT: Mathematical and computational modeling is in demand to help address current challenges in mechanobiology of musculoskeletal tissues. In particular for tendon, the high clinical importance of the tissue, the huge mechanical demands placed on it and its ability to adapt to these demands, require coupled, multiscale models incorporating complex geometrical and microstructural information as well as time-based descriptions of cellular activity and response.This review introduces the information sources required to develop such multiscale models. It covers tissue structure and biomechanics, cell biomechanics, the current understanding of tendon's ability in health and disease to update its properties and structure and the few already existing multiscale mechanobiological models of the tissue. Finally, a sketch is provided of what such models could achieve ideally, pointing out where experimental data and knowledge are still missing.
    Bulletin of Mathematical Biology 05/2013; 75(8). DOI:10.1007/s11538-013-9850-5 · 1.39 Impact Factor
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    • "In vitro, the type and axis of loading of bioscaffolds affect the cellular response. Compression loading leads to the formation of more cartilaginous tissue, whereas shear stress produces increased matrix metalloproteinases (MMP-1 and 3) in rabbit tendon fibroblasts, which results in matrix disruption [83, 84]. Repetitive loading, at higher construct strains, results in production of PGE2 and BMP2, leading to differentiation into nontendon lineages [85, 86]. "
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    ABSTRACT: Tendon injuries are a common cause of morbidity and a significant health burden on society. Tendons are structural tissues connecting muscle to bone and are prone to tearing and tendinopathy, an overuse or degenerative condition that is characterized by failed healing and cellular depletion. Current treatments, for tendon tear are conservative, surgical repair or surgical scaffold reconstruction. Tendinopathy is treated by exercises, injection therapies, shock wave treatments or surgical tendon debridement. However, tendons usually heal with fibrosis and scar tissue, which has suboptimal tensile strength and is prone to reinjury, resulting in lifestyle changes with activity restriction. Preclinical studies show that cell therapies have the potential to regenerate rather than repair tendon tissue, a process termed tenogenesis. A number of different cell lines, with varying degrees of differentiation, have being evaluated including stem cells, tendon derived cells and dermal fibroblasts. Even though cellular therapies offer some potential in treating tendon disorders, there have been few published clinical trials to determine the ideal cell source, the number of cells to administer, or the optimal bioscaffold for clinical use.
    01/2012; 2012(318):637836. DOI:10.1155/2012/637836
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    • "However, even at high fluid-shear rates and with the induction of collagenase, there is no significant calcium influx in tendon cells (Archambault et al. 2002). Thus, gene expression may be activated through different mechanotransduction mechanisms (kinases, stretch-activated ion channels) depending on the mechanical signal experienced by the cell (Archambault et al. 2002). Indeed, kinases are cell membrane proteins that are phosphorylated when subjected to cyclic stretching or shear stress (Arnoczky et al. 2002b; Iwasaki et al. 2000; Wang 2006). "
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    ABSTRACT: The importance of fluid-flow-induced shear stress and matrix-induced cell deformation in transmitting the global tendon load into a cellular mechanotransduction response is yet to be determined. A multiscale computational tendon model composed of both matrix and fluid phases was created to examine how global tendon loading may affect fluid-flow-induced shear stresses and membrane strains at the cellular level. The model was then used to develop a quantitative experiment to help understand the roles of membrane strains and fluid-induced shear stresses on the biological response of individual cells. The model was able to predict the global response of tendon to applied strain (stress, fluid exudation), as well as the associated cellular response of increased fluid-flow-induced shear stress with strain rate and matrix-induced cell deformation with strain amplitude. The model analysis, combined with the experimental results, demonstrated that both strain rate and strain amplitude are able to independently alter rat interstitial collagenase gene expression through increases in fluid-flow-induced shear stress and matrix-induced cell deformation, respectively.
    Biomechanics and Modeling in Mechanobiology 10/2007; 7(5):405-16. DOI:10.1007/s10237-007-0104-z · 3.15 Impact Factor
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