Substance P enhances collagen remodeling and MMP-3 expression by human tenocytes
Substance P enhances collagen remodeling and MMP-3 expression by human tenocytes
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DOI：
10.1002/jor.22191
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发表时间：
2013-01-01
影响因子：
2.8
通讯作者：
Scott, Alex
中科院分区：
文献类型：
--
作者：
Fong, Gloria;Backman, Ludvig J.;Scott, Alex
胶原组织的丢失被认为是肌腱病的一个显著的组织病理学特征。在细胞水平上，腱细胞被证明可以产生曾经被认为仅限于神经元的信号物质。P物质(SP)是肌腱病的主要神经肽之一，它能影响胶原组织，尤其是在损伤后。本研究的目的是观察SP对原代培养的人肌腱细胞在三维胶原网中胶原重构的影响。我们发现，SP的刺激通过神经激肽-1受体(NK-1R)介导的胶原重塑的速率增加，NK-1R是SP的首选细胞受体。基因表达分析显示，SP刺激后胶原网中MMP3、COL3A1和ACTA2基因表达水平显著升高。此外，肌腱细胞培养的循环拉伸负荷和外源性SP对MMP3的表达有相加的影响。免疫印迹法证实，SP通过NK-1R增加MMP3蛋白水平。本研究表明，SP通过NK-1R促进胶原重构，并导致MMP3mRNA和蛋白表达增加，而周期性机械负荷进一步增强了MMP3的表达。(C)2012年骨科研究会。由Wiley期刊公司出版，J Orthop Res 31：9198,2012
The loss of collagen organization is considered a hallmark histopathologic feature of tendinosis. At the cellular level, tenocytes have been shown to produce signal substances that were once thought to be restricted to neurons. One of the main neuropeptides implicated in tendinosis, substance P (SP), is known to influence collagen organization, particularly after injury. The aim of this study was to examine the influence of SP on collagen remodeling by primary human tendon cells cultured in vitro in three-dimensional collagen lattices. We found that SP stimulation led to an increased rate of collagen remodeling mediated via the neurokinin-1 receptor (NK-1 R), the preferred cell receptor for SP. Gene expression analysis showed that SP stimulation resulted in significant increases in MMP3, COL3A1 and ACTA2 mRNA levels in the collagen lattices. Furthermore, cyclic tensile loading of tendon cell cultures along with the administration of exogenous SP had an additive effect on MMP3 expression. Immunoblotting confirmed that SP increased MMP3 protein levels via the NK-1 R. This study indicates that SP, mediated via NK-1 R, increases collagen remodeling and leads to increased MMP3 mRNA and protein expression that is further enhanced by cyclic mechanical loading. (c) 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:9198, 2012