Experimental Mouse Model of Lumbar Ligamentum Flavum Hypertrophy.
Experimental Mouse Model of Lumbar Ligamentum Flavum Hypertrophy.
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DOI：
10.1371/journal.pone.0169717
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Okada S
中科院分区：
文献类型：
--
作者：
Saito T;Yokota K;Kobayakawa K;Hara M;Kubota K;Harimaya K;Kawaguchi K;Hayashida M;Matsumoto Y;Doi T;Shiba K;Nakashima Y;Okada S
腰椎管狭窄症（LSCS）是老年人最常见的脊柱疾病之一，随着人口老龄化，LSCS患者的数量不断增加。黄韧带（LF）是位于椎管内部的脊柱韧带，并且导致神经根和/或马尾的直接压迫的LF肥大是LSCS的主要原因。虽然有以前的研究LF肥大，其病理机制仍不清楚。本研究的目的是建立一个相关的小鼠LF肥大模型，并探讨疾病相关因素。首先，我们专注于机械应力，并开发了一种加载装置，用于对小鼠LF施加连续的机械屈伸应力。在12周的机械应力加载后，我们发现，与对照组相比，应力组的LF厚度显著增加。此外，胶原纤维面积、LF细胞数量和几种纤维化相关因子的基因表达均显著增加。然而，在这种机械应激模型中，没有巨噬细胞浸润、血管生成或转化生长因子-β1（TGF-β1）表达增加，这些是LSCS患者LF肥大特征性特征。因此，我们研究了浸润性巨噬细胞对LF肥大的影响。微损伤小鼠LF诱导巨噬细胞浸润后，伤后2周发现损伤部位胶原过度合成，TGF-β1表达增加，伤后6周进一步证实LF肥大。我们的研究结果表明，机械应力是LF肥大的一个致病因素，并强烈建议通过刺激胶原蛋白的产生，在LF肥大的进展中的巨噬细胞浸润的重要性。
Lumbar spinal canal stenosis (LSCS) is one of the most common spinal disorders in elderly people, with the number of LSCS patients increasing due to the aging of the population. The ligamentum flavum (LF) is a spinal ligament located in the interior of the vertebral canal, and hypertrophy of the LF, which causes the direct compression of the nerve roots and/or cauda equine, is a major cause of LSCS. Although there have been previous studies on LF hypertrophy, its pathomechanism remains unclear. The purpose of this study is to establish a relevant mouse model of LF hypertrophy and to examine disease-related factors. First, we focused on mechanical stress and developed a loading device for applying consecutive mechanical flexion-extension stress to the mouse LF. After 12 weeks of mechanical stress loading, we found that the LF thickness in the stress group was significantly increased in comparison to the control group. In addition, there were significant increases in the area of collagen fibers, the number of LF cells, and the gene expression of several fibrosis-related factors. However, in this mecnanical stress model, there was no macrophage infiltration, angiogenesis, or increase in the expression of transforming growth factor-β1 (TGF-β1), which are characteristic features of LF hypertrophy in LSCS patients. We therefore examined the influence of infiltrating macrophages on LF hypertrophy. After inducing macrophage infiltration by micro-injury to the mouse LF, we found excessive collagen synthesis in the injured site with the increased TGF-β1 expression at 2 weeks after injury, and further confirmed LF hypertrophy at 6 weeks after injury. Our findings demonstrate that mechanical stress is a causative factor for LF hypertrophy and strongly suggest the importance of macrophage infiltration in the progression of LF hypertrophy via the stimulation of collagen production.
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影响因子：
4.5
作者：
Kalichman, Leonid;Cole, Robert;Kim, David H.;Li, Ling;Suri, Pradeep;Guermazi, Ali;Hunter, David J.
通讯作者：
Hunter, David J.
影响因子：
--
作者：
Lakemeier, Stefan;Schofer, Markus D.;Foelsch, Christian
通讯作者：
Foelsch, Christian
影响因子：
4.9
作者：
Nagai T;Sato M;Kutsuna T;Kokubo M;Ebihara G;Ohta N;Mochida J
通讯作者：
Mochida J
影响因子：
6
作者：
Lewindon, PJ;Pereira, TN;Ramm, GA
通讯作者：
Ramm, GA
影响因子：
3
作者：
Kosaka, Hirofumi;Sairyo, Koichi;Yasui, Natsuo
通讯作者：
Yasui, Natsuo