Abstract
BackgroundMechanical loading plays an important role in the regulation of extracellular matrix (ECM) homeostasis as well as pathogenesis of intervertebral disc (IVD) degeneration. The human annulus fibrosus (hAF) in the IVD is subjected to contact shear stress during body motion. However, the effects of shear stress on hAF cells remain unclear. This aim of the study was to investigate the expression of the ECM (COLI, COLIII and aggrecan) and matrix metalloproteinase (MMP-1, MMP-3 and ADAMTS-4) genes in hAF cells following fluid-induced shear stress in a custom-fabricated bio-microfluidic device.MethodshAF cells were harvested from degenerated disc tissues in routine spine surgery, staged by magnetic resonance imaging, expanded in monolayers and then seeded onto the bio-microfluidic device. The experimental groups were subjected to 1 and 10 dyne/cm2 shear stress for 4 h, and no shear stress was applied to the control group. We used real time polymerase chain reaction for gene expression.ResultsShear stress of 1 dyne/cm2 exerted an anabolic effect on COLI and COLIII genes and catabolic effects on the aggrecan gene, while 10 dyne/cm2 had an anabolic effect on the COLI gene and a catabolic effect on COLIII and aggrecan genes. The COLI gene was upregulated in a stress-dependent manner. Expression of MMP-1 was significantly higher in the 10 dyne/cm2 group compared to the control group (P < 0.05), but was similar in the control and 1 dyne/cm2 groups. Expression of MMP-3 and ADAMTS-4 were similar in all three groups.ConclusionTaken together, hAF cells responded to shear stress. The findings help us understand and clarify the effects of shear stress on IVD degeneration as well as the development of a new therapeutic strategy for IVD degeneration.
Highlights
Mechanical loading plays an important role in the regulation of extracellular matrix (ECM) homeostasis as well as pathogenesis of intervertebral disc (IVD) degeneration
IVD degeneration is characterized by increased degradation of the extracellular matrix (ECM) by locally produced matrix metalloproteinases (MMPs) and aggrecanase which belongs to the ADAMTS family [1, 9]
We investigated the effects of fluidinduced shear stress on the expression of ECM genes (COLI, COLIII and aggrecan), and MMP genes (MMP-1, MMP-3, and ADAMTS-4) of human annulus fibrosus (hAF) cells harvested from degenerated disc tissues in a custom-fabricated biomicrofluidic device
Summary
Mechanical loading plays an important role in the regulation of extracellular matrix (ECM) homeostasis as well as pathogenesis of intervertebral disc (IVD) degeneration. The human annulus fibrosus (hAF) in the IVD is subjected to contact shear stress during body motion. The effects of shear stress on hAF cells remain unclear. A number of mechanical factors such as tension [6], compression [7], shear stress [3] and vibration [8] as well as other factors such as aging, genetic and systemic factors have been implicated in the pathogenesis of IVD degeneration [5]. IVD degeneration is characterized by increased degradation of the extracellular matrix (ECM) by locally produced matrix metalloproteinases (MMPs) and aggrecanase which belongs to the ADAMTS family (a disintegrin and metalloproteinase with thrombospondin motifs) [1, 9]. Collagens and aggrecans, which are the major components of the ECM in the IVD, are synthesized by the IVD, and broken down by MMPs and aggrecanases [5] to achieve dynamic equilibrium
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