Department of Orthopedic, General Hospital of Ningxia Medical University Yinchuan, Ningxia Hui Autonomous Region, 750004, China; Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, 750004, China.
Department of Surgery Laboratory, Institute of Medical Sciences, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, China.
Tuberculosis (Edinb). 2024 Sep;148:102546. doi: 10.1016/j.tube.2024.102546. Epub 2024 Jul 18.
Spinal Tuberculosis (STB) is a common cause of spinal malformation caused by extrapulmonary tuberculosis in developing countries, which seriously affects the quality of life of patients. It was found that the expression of miRNAs in macrophages was stable, specific and readily available after Mycobacterium tuberculosis (MTB) infection. Our research group determined the differential expression of miR-29a-3p in the vertebra of spinal tuberculosis and intervertebral disc lesions through RNAs chip screening and bioinformatics analysis. However, the specific molecular mechanism of miR-29a-3p in the inflammatory response of spinal tuberculosis remains unclear.
In this study, we mainly discussed the expression of miR-29a-3p in the focal tissue of spinal tuberculosis and the role and molecular mechanism of miR-29a-3p mediated by METTL3 in the inflammatory response of spinal tuberculosis.
The tissues of 15 cases of lumbar degenerative diseases and vertebral lesions of spinal tuberculosis were collected, and the THP-1 macrophage model infected by Mycobacterium tuberculosis was constructed, and verified by qRT-PCR, Western blot, fluorescence in situ hybridization, immunohistochemistry, Cell fluorescence and ELISA.
We found that the expression of miR-29a-3p was significantly down-regulated in the vertebral body and disc lesion tissues of patients with spinal tuberculosis. Overexpression of miR-29a-3p inhibited the levels of inflammatory factors including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6), and inhibition of miR-29a-3p expression promoted the release of the levels of TNF-α, IL-1β and IL-6 inflammatory factors. Our study also shows that knockout of methyltransferase 3 (METTL3) can significantly reduce the expression of miR-29a-3p and promote the release of pro-inflammatory cytokines in macrophages.
脊柱结核（STB）是发展中国家肺外结核引起的常见脊柱畸形原因，严重影响患者的生活质量。研究发现，分枝杆菌（MTB）感染后巨噬细胞中 miRNA 的表达稳定、特异且易于获得。我们的研究小组通过 RNA 芯片筛选和生物信息学分析，确定了 miR-29a-3p 在脊柱结核椎骨和椎间盘病变中的差异表达。然而，miR-29a-3p 在脊柱结核炎症反应中的具体分子机制尚不清楚。
本研究主要探讨 miR-29a-3p 在脊柱结核病灶组织中的表达，以及 METTL3 介导的 miR-29a-3p 在脊柱结核炎症反应中的作用及其分子机制。
收集 15 例腰椎退行性疾病和脊柱结核椎骨病变组织，构建分枝杆菌感染的 THP-1 巨噬细胞模型，通过 qRT-PCR、Western blot、荧光原位杂交、免疫组织化学、细胞荧光和 ELISA 进行验证。
①研究发现，脊柱结核患者椎体和椎间盘病变组织中 miR-29a-3p 的表达明显下调；②过表达 miR-29a-3p 抑制肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）等炎症因子水平，抑制 miR-29a-3p 表达促进 TNF-α、IL-1β 和 IL-6 炎症因子的释放；③研究还表明，敲除甲基转移酶 3（METTL3）可显著降低 miR-29a-3p 的表达，促进巨噬细胞中促炎细胞因子的释放。
综上所述，该研究结果表明，METTL3 可能通过调控 miR-29a-3p 表达促进脊柱结核炎症反应。
