The role of osteopontin in tendon tissue remodeling after denervation-induced mechanical stress deprivation
The role of osteopontin in tendon tissue remodeling after denervation-induced mechanical stress deprivation
复制标题
DOI：
10.1016/j.matbio.2006.09.002
复制
发表时间：
2007-01-01
期刊：
影响因子：
6.9
通讯作者：
Uede, Toshimitsu
中科院分区：
文献类型：
--
作者：
Mori, Noriaki;Majima, Tokifumi;Uede, Toshimitsu
研究表明，肌肉骨骼组织通过一个对机械环境相当敏感的过程进行动态组织重塑。然而，这一过程背后的详细分子机制尚不清楚。我们在这里证明，在去神经支配诱导的机械应力剥夺后，肌腱经历动态组织重塑，胶原纤维直径显著减少。重要的是，骨桥蛋白（OPN）表达的短暂上调是肌腱组织重塑早期的特征。随着OPN表达的这种动态变化，基质金属蛋白酶（matrix metalloproteinase， MMP）-13被诱导表达，这可能是通过降解肌腱胶原原纤维导致肌腱形态变化的原因。OPN对MMP-13表达的调节是特异性的，因为在没有或存在OPN的情况下，肌腱中MMP-2的表达没有改变，而MMP-2也参与组织重塑。我们还证明了OPN对MMP-13表达的调节是由于OPN通过细胞表面受体的信号传导。因此，我们得出结论，OPN通过调节肌腱成纤维细胞中MMP-13的表达，在将去神经支配诱导的机械应力剥夺作用传递给肌腱成纤维细胞以降解细胞外基质方面起着至关重要的作用。(c) 2006 Elsevier B.V./International Society of Matrix Biology。版权所有。
It has been shown that musculoskeletal tissues undergo dynamic tissue remodeling by a process that is quite sensitive to the mechanical environment. However, the detailed molecular mechanism underlying this process remains unclear. We demonstrate here that after denervation-induced mechanical stress deprivation, tendons undergo dynamic tissue remodeling as evidenced by a significant reduction of the collagen fibril diameter. Importantly, the transient up-regulation of osteopontin (OPN) expression was characteristic during the early phase of tendon tissue remodeling. Following this dynamic change of OPN expression, matrix metalloproteinase (MMP)-13 expression was induced, which presumably accounts for the morphological changes of tendon by degrading tendon collagen fibrils. The modulation of MMP-13 expression by OPN was specific, since the expression of MMP-2, which is also known to be involved in tissue remodeling, did not alter in the tendons under the absence or presence of OPN. We also demonstrate that the modulation of MMP-13 expression by OPN is due to the signaling through cell surface receptors for OPN. Thus, we conclude that OPN plays a crucial role in conveying the effect of denervation-induced mechanical stress deprivation to the tendon fibroblasts to degrade the extracellular matrices by regulating MMP-13 expression in tendon fibroblasts. (c) 2006 Elsevier B.V./International Society of Matrix Biology. All rights reserved.