椎间盘（IVD）退变是导致 IVD 细胞活性失调的多因素病理过程。 IVD 细胞在变性过程中观察到的分解代谢转变会导致炎症加剧、细胞外基质 (ECM) 降解、细胞内信号传导异常和细胞损失。重要的是，已知这些病理过程是相互关联的并共同促进疾病的进展。 MicroRNA (miRNA) 被称为强大的转录后调节因子，同时针对多个基因并调节许多细胞内途径。具体而言，miR-155-5p 引起了人们的特别关注，因为它被认为是一种促炎介质，也是癌症和骨关节炎等疾病的促成因素。本研究调查了 miR-155-5p 在 IVD 变性中的作用，特别关注炎症和机械传感。通过转染人髓核 (NP) 和纤维环 (AF) 细胞进行功能获得和丧失研究从退化的 IVD 中分离出 miR-155-5p 模拟物、抑制剂或其相应的非靶向对照。然后将转染的细胞置于炎症环境或机械负荷下。收集条件培养基和细胞裂解物用于磷酸化和细胞因子分泌阵列以及基因表达分析。AF 细胞中 miR-155-5p 表达增加导致循环拉伸期间白细胞介素 (IL)-8 细胞因子分泌显着上调和类似的情况。炎症期间IL-6分泌的趋势。此外，miR-155-5p模拟物增加了经历循环拉伸的AF细胞中脑源性神经营养因子（BDNF）的表达。在 NP 细胞中，miR-155-5p 的功能获得通过增加 p38 和 p53 的磷酸化导致丝裂原激活蛋白激酶 (MAPK) 信号通路的激活。最后，抑制 miR-155-5p 分别导致 AF 细胞中的抗炎细胞因子 IL-10 和 NP 细胞中的金属蛋白酶组织抑制剂 (TIMP)-4 显着增加。总的来说，这些结果表明 miR-155- 5p 通过促炎细胞因子和 MAPK 信号传导增强炎症，以及在机械负荷过程中促进 AF 细胞的分解代谢转变，从而导致 IVD 变性。抑制 miR-155-5p 可能构成 IVD 变性和腰痛的潜在治疗方法。© 2024。作者。

Intervertebral disc (IVD) degeneration is a multifactorial pathological process resulting in the dysregulation of IVD cell activity. The catabolic shift observed in IVD cells during degeneration leads to increased inflammation, extracellular matrix (ECM) degradation, aberrant intracellular signaling and cell loss. Importantly, these pathological processes are known to be interconnected and to collectively contribute to the progression of the disease. MicroRNAs (miRNAs) are known as strong post-transcriptional regulators, targeting multiple genes simultaneously and regulating numerous intracellular pathways. Specifically, miR-155-5p has been of particular interest since it is known as a pro-inflammatory mediator and contributing factor to diseases like cancer and osteoarthritis. This study investigated the role of miR-155-5p in IVD degeneration with a specific focus on inflammation and mechanosensing.Gain- and loss-of-function studies were performed through transfection of human Nucleus pulposus (NP) and Annulus fibrosus (AF) cells isolated from degenerated IVDs with miR-155-5p mimics, inhibitors or their corresponding non-targeting control. Transfected cells were then subjected to an inflammatory environment or mechanical loading. Conditioned media and cell lysates were collected for phosphorylation and cytokine secretion arrays as well as gene expression analysis.Increased expression of miR-155-5p in AF cells resulted in significant upregulation of interleukin (IL)-8 cytokine secretion during cyclic stretching and a similar trend in IL-6 secretion during inflammation. Furthermore, miR-155-5p mimics increased the expression of the brain-derived neurotrophic factor (BDNF) in AF cells undergoing cyclic stretching. In NP cells, miR-155-5p gain-of-function resulted in the activation of the mitogen-activated protein kinase (MAPK) signaling pathway through increased phosphorylation of p38 and p53. Lastly, miR-155-5p inhibition caused a significant increase in the anti-inflammatory cytokine IL-10 in AF cells and the tissue inhibitor of metalloproteinases (TIMP)-4 in NP cells respectively.Overall, these results show that miR-155-5p contributes to IVD degeneration by enhancing inflammation through pro-inflammatory cytokines and MAPK signaling, as well as by promoting the catabolic shift of AF cells during mechanical loading. The inhibition of miR-155-5p may constitute a potential therapeutic approach for IVD degeneration and low back pain.© 2024. The Author(s).