Cyclic tensile strain facilitates ossification of the cervical posterior longitudinal ligament via increased Indian hedgehog signaling
Cyclic tensile strain facilitates ossification of the cervical posterior longitudinal ligament via increased Indian hedgehog signaling
复制标题
循环拉伸应变通过增加印度刺猬信号促进颈椎后纵韧带骨化
DOI：
10.1038/s41598-020-64304-w
复制
发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Matsumine A.
中科院分区：
文献类型：
--
作者：
Sugita D;Nakajima H;Kokubo Y;Takeura N;Yayama T;Matsumine A.
后纵韧带骨化的发生和发展的病理机制尚不清楚。Indian hedgehog（Ihh）及其相关信号分子是正常软骨骨化的关键因子。本研究的目的是探讨机械应变对OPLL的贡献以及Ihh与OPLL的关系。后纵韧带（PLL）的部分，从49例OPLL和7例无OPLL的患者。使培养的PLL细胞经受24小时的循环拉伸应变。为了鉴定与循环拉伸应变相关的差异表达基因，进行了微阵列分析。京都基因和基因组百科全书（KEGG）分析鉴定了各种基因的上调，特别是Hedgehog信号传导途径的上调;在24小时循环拉伸应变后，与对照相比，Ihand相关基因的表达增加。在免疫印迹分析中，Ihh、Runx 2、Sox 9、Gli 2、Gli 3和smoothened（SMO）在6或12小时循环拉伸应变后表达显著增加。OPLL样品在OPLL的骨化前沿中对Ihh、Sox 9、Runx 2、Gli 2、Gli 3和SMO呈强免疫阳性。这些结果表明，周期性张应变会诱导Ihh和相关信号分子的异常激活，这可能在OPLL的成骨过程中很重要。
The pathomechanisms of initiation and progression of ossification of the posterior longitudinal ligament (OPLL) are unclear. Indian hedgehog (Ihh) and related signaling molecules are key factors in normal enchondral ossification. The purpose of this study is to investigate the contribution of mechanical strain to OPLL and the relationship of Ihh with OPLL. Sections of the posterior longitudinal ligament (PLL) were obtained from 49 patients with OPLL and from 7 patients without OPLL. Cultured PLL cells were subjected to 24 hours of cyclic tensile strain. To identify differentially expressed genes associated with cyclic tensile strain, microarray analysis was performed. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified upregulation of various genes, particularly of the Hedgehog signaling pathway;Ihhand related genes had increased expression compared with controls after 24-hour cyclic tensile strain. In immunoblotting analysis, Ihh, Runx2, Sox9, Gli2, Gli3, and smoothened (SMO) had significantly increased expression after 6- or 12-hour cyclic tensile strain. OPLL samples were strongly immunopositive for Ihh, Sox9, Runx2, Gli2, Gli3, and SMO in the ossification front of OPLL. These results suggest that cyclic tensile strain induces abnormal activation of Ihh and related signaling molecules, and this might be important in the ossification process in OPLL.