Cartilage intermediate layer protein promotes lumbar disc degeneration
Cartilage intermediate layer protein promotes lumbar disc degeneration
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DOI：
10.1016/j.bbrc.2014.03.025
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发表时间：
2014-04-18
影响因子：
3.1
通讯作者：
Kimura, Tomoatsu
中科院分区：
文献类型：
--
作者：
Seki, Shoji;Tsumaki, Noriyuki;Kimura, Tomoatsu
腰椎间盘疾病(LDD)是最常见的肌肉骨骼疾病之一，并伴有椎间盘退变。CILP编码软骨中间层蛋白，与腰椎间盘突出症密切相关。此外，CILP通过与转化生长因子-β1结合并抑制Smads的磷酸化，在体外抑制髓核细胞中软骨基质基因的转录激活。然而，LDD在体内的病因和发病机制尚不清楚。为了证明CILP在体内LDD中的作用，我们建立了在椎间盘组织中特异性表达CILP的转基因小鼠，并评估了CILP是否加剧了椎间盘退变。用磁共振成像(MRI)和组织学方法评估椎间盘退变情况。检测椎间盘中Smad2/3的磷酸化水平，以确定过表达的CILP是否抑制了转化生长因子-β信号转导。尽管转基因小鼠的宏观骨骼表型看起来正常，但组织学结果显示腰椎间盘显著退变。对腰椎间盘的MRI分析显示，CILP过度表达的髓核信号强度显著降低。同时还观察到了椎间盘退变。CILP转基因小鼠与正常小鼠相比，NP区Smad2/3免疫阳性细胞的磷酸化数量明显减少。综上所述，CILP在NP中的过表达促进了腰椎间盘退变，表明CILP在LDD的发病机制中起着直接作用。(C)2014 Elsevier Inc.保留所有权利。
Lumbar disc disease (LDD) is one of the most common musculoskeletal disorders, and accompanies intervertebral disc degeneration. CILP encodes cartilage intermediate layer protein, which is highly associated with LDD. Moreover, CILP inhibits transcriptional activation of cartilage matrix genes in nucleus pulposus (NP) cells in vitro by binding to TGF-beta 1 and inhibiting the phosphorylation of Smads. However, the aetiology and mechanism of pathogenesis of LDD in vivo are unknown. To demonstrate the role of CILP in LDD in vivo, we generated transgenic mice that express CILP specifically in the intervertebral disc tissues and assessed whether CILP exacerbates disc degeneration. Degeneration of the intervertebral discs was assessed using magnetic resonance imaging (MRI) and histology. The level of phosphorylation of Smad2/3 in intervertebral discs was measured to determine whether overexpressed CILP suppressed TGF-beta signalling. Although the macroscopic skeletal phenotype of transgenic mice appeared normal, histological findings revealed significant degeneration of lumbar discs. MRI analysis of the lumbar intervertebral discs indicated a significantly lower signal intensity of the nucleus pulposus where CILP was overexpressed. Intervertebral disc degeneration was also observed. The number of phosphorylation of Smad2/3 immuno-positive cells in the NP significantly was decreased in CILP transgenic mice compared with normal mice. In summary, overexpression of CILP in the NP promotes disc degeneration, indicating that CILP plays a direct role in the pathogenesis of LDD. (C) 2014 Elsevier Inc. All rights reserved.