Arnoczky Steven P, Lavagnino Michael, Egerbacher Monika, Caballero Oscar, Gardner Keri, Shender Marisa A
Laboratory for Comparative Orthopaedic Research, College of Veterinary Medicine, G-387, Michigan State University, East Lansing, MI, USA.
Clin Orthop Relat Res. 2008 Jul;466(7):1583-91. doi: 10.1007/s11999-008-0264-x. Epub 2008 May 6.
Tendon cells respond to mechanical loads. The character (anabolic or catabolic) and sensitivity of this response is determined by the mechanostat set point of the cell, which is governed by the cytoskeleton and its interaction with the extracellular matrix. To determine if loss of cytoskeletal tension following stress deprivation decreases the mechanoresponsiveness of tendon cells, we cultured rat tail tendons under stress-deprived conditions for 48 hours and then cyclically loaded them for 24 hours at 1%, 3%, or 6% strain at 0.17 Hz. Stress deprivation upregulated MMP-13 mRNA expression and caused progressive loss of cell-matrix contact compared to fresh controls. The application of 1% strain to fresh tendons for 24 hours inhibited MMP-13 mRNA expression compared to stress-deprived tendons over the same period. However, when tendons were stress-deprived for 48 hours and then subjected to the same loading regime, the inhibition of MMP-13 mRNA expression was decreased. In stress-deprived tendons, it was necessary to increase the strain magnitude to 3% to achieve the same level of MMP-13 mRNA inhibition seen in fresh tendons exercised at 1% strain. The data suggest loss of cytoskeletal tension alters the mechanostat set point and decreases the mechanoresponsiveness of tendon cells.
肌腱细胞对机械负荷产生反应。这种反应的特征（合成代谢或分解代谢）和敏感性由细胞的机械感受器设定点决定，该设定点受细胞骨架及其与细胞外基质的相互作用控制。为了确定应激剥夺后细胞骨架张力的丧失是否会降低肌腱细胞的机械反应性，我们将大鼠尾腱在应激剥夺条件下培养48小时，然后以0.17Hz的频率在1%、3%或6%的应变下对其进行24小时的循环加载。与新鲜对照组相比，应激剥夺上调了MMP-13 mRNA的表达，并导致细胞与基质接触的逐渐丧失。与同期应激剥夺的肌腱相比，对新鲜肌腱施加1%的应变24小时可抑制MMP-13 mRNA的表达。然而，当肌腱应激剥夺48小时后再进行相同的加载方案时，MMP-13 mRNA表达的抑制作用减弱。在应激剥夺的肌腱中，有必要将应变幅度提高到3%，以达到在1%应变下运动的新鲜肌腱中所见的相同水平的MMP-13 mRNA抑制。数据表明，细胞骨架张力的丧失改变了机械感受器设定点，并降低了肌腱细胞的机械反应性。
