HMGB1调控因子—miRNA的筛选及对椎间盘软骨终板退变自噬机制的研究

椎间盘退变性疾病是脊柱外科临床诊断中最常见的病种。研究发现软骨终板退变是导致椎间盘退变的始动因素，探讨软骨终板退变机制对于延缓或治疗椎间盘退变性疾病具有重要意义。高迁移率蛋白B1（HMGB1）作为晚期细胞炎症因子，与椎间盘软骨终板退变密切相关，但其表达调控机制尚不明确。miRNA可通过调控靶基因的转录在细胞的增殖分化、凋亡等生命活动中起重要调节作用。椎间盘退变被发现与细胞自噬存在紧密联系，但椎间盘软骨终板退变中的自噬还未报道。本项目采用生物学数据库和分子生物学方法初步确定调控HMGB1表达的4个miRNA, miR-34a，miR-181a，miR-129-5p，miR-142-3p。后续将利用动物原代软骨终板细胞模型和椎间失稳软骨终板退变模型，通过影像学、组织化学、细胞生物学和分子生物学等多种观察和检测手段，探究miRNA/HMGB1之间的调控机制并阐明影响软骨终板细胞自噬的作用机理。

Intervertebral disc degeneration is the most common diseases in clinical practice of the spine surgery. Present studies found the cartilage degeneration is the leading cause for disc degeneration, and to exploring the mechanism of cartilage endplate degeneration is meaningful for disease which is caused by disc degeneration. High mobility group protein box1 (HMGB1), as a late cell inflammatory factor, has been closely related to the degeneration of disc cartilage endplate, but the mechanism for regulating HMGB1 expression is not clear. MicRNAs (miRNA) play a crucial regulaotry role in proliferation and apoptosis of cells via regulating the transcription of the target genes. Intervertebral disc degeneration was found to be closely related to autophagy, but autophagy in degeneration of intervertebral disc cartilage endplates has not been reported. In this project, four miRNAs miR-34a, miR-181a, miR-129-5p, miR-142-3p are identified using biological databases and molecular biological methods. Furthermore, the project will establish primary cartilage endplate cell model and an animal intervertebral destabilization model which may induce cartilage endplate degeneration. Based on two models, imageological, histochemical, cellular biological and molecular biological methods will be performed to explore the effect and mechanism of miRNA/HMGB1 pathway on autophagy of intervertebral disc cartilage endplate degeneration.