Static compression induces zonal-specific changes in gene expression for extracellular matrix and cytoskeletal proteins in intervertebral disc cells in vitro.

Abstract

Compressive stimuli associated with weight-bearing and loading of the intervertebral disc are believed to be important regulators of disc cell metabolism. In this study, changes in gene expression levels for extracellular matrix and cytoskeletal proteins were quantified in disc cells in an alginate culture system subjected to static unconfined compression (25% compressive strain) after different time periods (2, 18 and 30 h). Differences in gene expression were observed between anulus fibrosus and nucleus pulposus cells following static compression for the matrix proteins studied here. Anulus fibrosus cells responded to mechanical deformation at the 30-h time point, with increasing gene expression for types I and II collagen, aggrecan, biglycan, decorin and lumican. In contrast, nucleus pulposus cells were not responsive to mechanical loading with changes in gene expression for these matrix proteins at any time. Our results also show that anulus fibrosus cells, but not nucleus pulposus cells, responded to static compression with increased expression of vimentin mRNA as well as increased polymerization of vimentin subunits. The results of the current study illustrate that fibrochondrocytes of the anulus fibrosus may regulate biosynthesis at the transcriptional level following mechanical deformation in an alginate construct. In contrast, the biological response of nucleus pulposus cells to these same stimuli is not detectable. These differences may be attributed to the presence of a notochordal cell population in the immature nucleus pulposus studied here, with a more diffuse and stiff cytoskeleton that may restrict deformations or shape changes upon compressive loading.