Qi Jie, Fox Ann Marie, Alexopoulos Leonidas G, Chi Liqun, Bynum Donald, Guilak Farshid, Banes Albert J
Flexcell International Corp., 437 Dimmocks Mill Rd., Suite 28, Hillsborough, North Carolina 27278, USA.
J Appl Physiol (1985). 2006 Jul;101(1):189-95. doi: 10.1152/japplphysiol.01128.2005. Epub 2006 Apr 20.
Cellular responses to mechanical stimuli are regulated by interactions with the extracellular matrix, which, in turn, are strongly influenced by the degree of cell stiffness (Young's modulus). It was hypothesized that a more elastic cell could better withstand the rigors of remodeling and mechanical loading. It was further hypothesized that interleukin-1beta (IL-1beta) would modulate intracellular cytoskeleton polymerization and regulate cell stiffness. The purpose of this study was to investigate the utility of IL-1beta to alter the Young's modulus of human tenocytes. Young's modulus is the ratio of the stress to the strain, E = stress/strain = (F/A)/(deltaL/L0), where L0 is the equilibrium length, deltaL is the length change under the applied stress, F is the force applied, and A is the area over which the force is applied. Human tenocytes were incubated with 100 pM recombinant human IL-1beta for 5 days. The Young's modulus was reduced by 27-63%. Actin filaments were disrupted in >75% of IL-1beta-treated cells, resulting in a stellate shape. In contrast, immunostaining of alpha-tubulin showed increased intensity in IL-1beta-treated tenocytes. Human tenocytes in IL-1beta-treated bioartificial tendons were more tolerant to mechanical loading than were untreated counterparts. These results indicate that IL-1beta reduced the Young's modulus of human tenocytes by disrupting the cytoskeleton and/or downregulating the expression of actin and upregulating the expression of tubulins. The reduction in cell modulus may help cells to survive excessive mechanical loading that may occur in damaged or healing tendons.
细胞对机械刺激的反应是由与细胞外基质的相互作用所调节的，而细胞外基质又受到细胞刚度（杨氏模量）程度的强烈影响。据推测，弹性更强的细胞能够更好地承受重塑和机械负荷的严峻考验。进一步推测白细胞介素-1β（IL-1β）会调节细胞内细胞骨架的聚合并调节细胞刚度。本研究的目的是探讨IL-1β改变人肌腱细胞杨氏模量的效用。杨氏模量是应力与应变的比值，E = 应力/应变 = (F/A)/(ΔL/L0)，其中L0是平衡长度，ΔL是在施加应力下的长度变化，F是施加的力，A是力作用的面积。将人肌腱细胞与100 pM重组人IL-1β孵育5天。杨氏模量降低了27 - 63%。在超过75%的经IL-1β处理的细胞中，肌动蛋白丝被破坏，导致细胞呈星状。相比之下，α-微管蛋白的免疫染色显示在经IL-1β处理的肌腱细胞中强度增加。与未处理的对应物相比，经IL-1β处理的生物人工肌腱中的人肌腱细胞对机械负荷更具耐受性。这些结果表明，IL-1β通过破坏细胞骨架和/或下调肌动蛋白的表达以及上调微管蛋白的表达来降低人肌腱细胞的杨氏模量。细胞模量的降低可能有助于细胞在受损或愈合的肌腱中可能发生的过度机械负荷下存活。
