The effects of short-term load duration on anabolic and catabolic gene expression in the rat tail intervertebral disc (original) (raw)

2005, Journal of Orthopaedic Research

The goal of this study was to determine the time-dependent response of the intervertebral disc cells to in vivo dynamic compression. Forty-seven skeletally mature Wistar rats (> 12 months old) were instrumented with an Ilizarov-type device spanning caudal disc 8-9. Using a load magnitude (1 MPa) and frequency (1.0 Hz) that were previously shown to significantly alter mRNA levels in the disc, the effects of 0.5 and 4 h of loading were investigated and compared to a sham group and our previous 2 h results. Annulus and nucleus tissue of loaded (c8-9) and internal control discs ( c 6 7 and c10-11) were separately analyzed by real-time RT-PCR for levels of mRNA coding for various anabolic (collagen-lAl, collagen-2A1, aggrecan) and catabolic (MMP-3, MMP-13, ADAMTs-4) proteins. In the annulus, mRNA levels increased for Collagen types I & 11, and MMP 3 & 13 with increasing load duration. In contrast, the nucleus had the largest increases in aggrecan, ADAMTs-4, MMP-3 and MMP-13 after 2 h of loading, with aggrecan and MMP-13 mRNA levels returning to control values after 4 h of loading. Taken in context with our previous studies, we conclude that intervertebral disc cells from the nucleus and annulus have distinct responses to dynamic mechanical compression in vivo with sensitivity to compression magnitude, frequency and duration. (J.C. Iatridis). environment surrounding the cells. It is clear that the disc cells respond to mechanical stimuli, although the direct (i.e. physical deformation of cells and/or changes in the hydrostatic pressure) and indirect (i.e. by affecting nutrient transport or extracellular osmolarity and pH 12,) effects of mechanical loading on disc cell metabolism have not yet been wholly elicited. Specifically, the application of static loads have been shown to induce cell apoptosis and alter mechanical properties (disc thickness, axial compliance and angular laxity), matrix content (proteoglycan and type I and I1 collagen), metalloproteinase activity, and disc cell gene expression (aggrecan and collagen 11) [ 13,[16][17][19] 11, while changes in hydrostatic pressure have been found 0736-0266/$see front matter 0