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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。

Cyclic tensile strain facilitates ossification of the cervical posterior longitudinal ligament via increased Indian hedgehog signaling.

机构信息

Department of Orthopaedics and Rehabilitation Medicine, Faculty of Medical Sciences University of Fukui, 23-3 Matsuoka Shimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui, 910-1193, Japan.

Department of Orthopaedic Surgery, Shiga University of Medical Science, Setatsukiwachou, Otsu, Shiga, 520-2192, Japan.

出版信息

Sci Rep. 2020 Apr 29;10(1):7231. doi: 10.1038/s41598-020-64304-w.

DOI:10.1038/s41598-020-64304-w
PMID:32350355
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7190672/
Abstract

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; Ihh and 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.

摘要

后纵韧带骨化(OPLL)起始和进展的病理机制尚不清楚。印度刺猬(Ihh)和相关信号分子是正常软骨内骨化的关键因素。本研究旨在探讨机械应变对 OPLL 的贡献以及 Ihh 与 OPLL 的关系。从 49 例 OPLL 患者和 7 例无 OPLL 患者中获取后纵韧带(PLL)节段。培养 PLL 细胞,施加 24 小时循环拉伸应变。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。京都基因与基因组百科全书(KEGG)分析鉴定出各种基因的上调,特别是 Hedgehog 信号通路;与对照组相比,经过 24 小时循环拉伸应变后,Ihh 和相关基因的表达增加。在免疫印迹分析中,Ihh、Runx2、Sox9、Gli2、Gli3 和 smoothened(SMO)在 6 或 12 小时循环拉伸应变后表达显著增加。OPLL 样本在前 OPLL 的骨化前沿中 Ihh、Sox9、Runx2、Gli2、Gli3 和 SMO 呈强免疫阳性。这些结果表明,循环拉伸应变诱导 Ihh 和相关信号分子的异常激活,这可能在 OPLL 的骨化过程中很重要。

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异位骨化:当前进展与新兴潜在疗法
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