Chen Jun, Yan Wei, Setton Lori A
Department of Biomedical Engineering, Duke University, Box 90281, 136 Hudson Hall, Durham, NC 27708-0281, USA.
Matrix Biol. 2004 Jan;22(7):573-83. doi: 10.1016/j.matbio.2003.11.008.
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.
与椎间盘负重和负荷相关的压缩刺激被认为是椎间盘细胞代谢的重要调节因子。在本研究中，在藻酸盐培养系统中，对椎间盘细胞施加静态无侧限压缩（25%压缩应变），在不同时间段（2、18和30小时）后，对细胞外基质和细胞骨架蛋白的基因表达水平变化进行了定量分析。对于此处研究的基质蛋白，在静态压缩后，纤维环细胞和髓核细胞之间观察到基因表达差异。纤维环细胞在30小时时间点对机械变形有反应，I型和II型胶原蛋白、聚集蛋白聚糖、双糖链蛋白聚糖、核心蛋白聚糖和光蛋白聚糖的基因表达增加。相比之下，髓核细胞在任何时候对这些基质蛋白的基因表达变化对机械负荷均无反应。我们的结果还表明，纤维环细胞而非髓核细胞对静态压缩的反应是波形蛋白mRNA表达增加以及波形蛋白亚基聚合增加。本研究结果表明，在藻酸盐构建体中，纤维环的纤维软骨细胞在机械变形后可能在转录水平调节生物合成。相比之下，髓核细胞对这些相同刺激的生物学反应无法检测到。这些差异可能归因于此处研究的未成熟髓核中存在脊索细胞群体，其细胞骨架更弥散且僵硬，这可能会限制压缩负荷时的变形或形状变化。
