Institute for Science and Technology in Medicine, The Guy Hilton Research Centre, University of Keele, Stoke-on-Trent, Staffordshire, UK.
J Tissue Eng Regen Med. 2010 Oct;4(7):577-9. doi: 10.1002/term.293.
Mechanical forces, important in a variety of cellular processes, including proliferation, differentiation and gene expression, are also key in the development, remodelling and maintenance of load-bearing tissues such as cartilage and bone. Thus, there is great interest in using in vitro mechanical conditioning of mesenchymal stem cells (MSCs), multipotent adult stem cells, for tissue engineering of these tissues. In a previous gene expression study, we reported a potentially important role for mitogen-activated protein kinase kinase kinase 8 (MAP3K8) and interleukin-1β (IL-1B) in MAPK signalling in MSCs exposed to fluid shear stress. In this follow-up study, we examined the expression of these genes in MSCs exposed to other types of mechanical force: uniaxial tensile strain (3% cell elongation) and forces generated through the exposure of magnetic particle-labelled MSCs to an oscillating magnetic field (maximum field strength 90 mT). Exposure to both types of mechanical force for 1 h did not significantly alter the gene expression of MAP3K8 or IL-1B over the 24 h period subsequent to force exposure. These data demonstrate that uniaxial tensile strain and magnetic particle-based forces do not induce MAP3K8-related MAPK signalling in the same manner as does fluid flow-induced shear stress. This illustrates divergence in the process of mechanotransduction in mechanically stimulated MSCs.
机械力在多种细胞过程中很重要,包括增殖、分化和基因表达,它们也是软骨和骨骼等承重组织发育、重塑和维持的关键。因此,人们非常有兴趣使用体外机械条件培养间充质干细胞(MSCs),即多能成体干细胞,用于这些组织的组织工程。在之前的基因表达研究中,我们报告了丝裂原活化蛋白激酶激酶激酶 8(MAP3K8)和白细胞介素-1β(IL-1B)在 MSCs 暴露于流体剪切力时的 MAPK 信号传导中可能具有重要作用。在这项后续研究中,我们研究了这些基因在 MSCs 暴露于其他类型机械力时的表达:单轴拉伸应变(细胞伸长 3%)和通过暴露于振荡磁场的磁性粒子标记的 MSCs 产生的力(最大场强 90 mT)。在力暴露后的 24 小时内,暴露于这两种机械力 1 小时并没有显著改变 MAP3K8 或 IL-1B 的基因表达。这些数据表明,单轴拉伸应变和基于磁性粒子的力不会像流体流动诱导的剪切力那样诱导 MAP3K8 相关的 MAPK 信号传导。这说明了在机械刺激的 MSCs 中,机械转导过程的分歧。