Revisiting miR-155 in intervertebral disc degeneration: blood cell signature and local cell-free profiles

Zhiheng Liu,Haiqiang Wang,Zhen Sun,Zhongyuan Wan

doi:10.32604/biocell.2022.016194

Abstract

We unraveled the expression profiles of coding-noncoding RNAs in intervertebral disc degeneration (IDD). However, it remains elusive regarding miR-155 expression in peripheral blood mononuclear cells (PBMCs) and local extracellular space in IDD. The study aimed for investigating the miR-155 expression of PBMCs, extracellular miRNAs (ex-miRNAs) of human nucleus pulposus (NP) tissues, and morphological changes of cell death in the IDD process. Here, we harvested peripheral blood and NP samples from scoliosis and IDD patients as control and degenerative groups, respectively. Then standard Ficoll density-gradient centrifugation was used to isolate PBMCs. The two subpopulations of PBMCs were divided based on the cellular difference in adherence, i.e., monocytes/ macrophages and lymphocytes. Quantitative real-time PCR was used to evaluate miR-155 relative expression in PBMCs. ex-miRNAs were screened by comparison between GSE19943, GSE63492, and extracellular RNA (exRNA) atlas. The morphological changes of cell death subtypes in IDD were observed in transmission electron microscopy (TEM). Results indicate that the lower expression of miR-155 in PBMCs from IDD patients ascribed to alterations in monocytes/macrophages. Moreover, we identified 594 shared hsa-miRNAs as the intracellular miRNA expression profile and 258 miRNAs as the ex-miRNA expression profile in human NP tissue. miR-155 was amongst intracellular miRNAs in NP. TEM observation presented multiple endocytic secretory vesicles within human NP cells, implicating exosome transporting machinery. Typical necroptosis and pyroptosis were noted in human NP. Collectively, this study reveals miR-155 expression in PBMCs from IDD patients. Moreover, we propose ex-miRNA expression profile and necroptosis/pyroptosis in human NP tissue, shedding novel light on the etiology of IDD.

Highlights

As the chief cells in nucleus pulposus (NP) tissues, NP cells contribute significantly to the development of intervertebral disc degeneration (IDD), which is the leading cause of low back pain (Richardson et al, 2017)
peripheral blood mononuclear cells (PBMCs) collection and subpopulation division PBMCs were isolated from blood samples of patients with idiopathic scoliosis, and IDD followed standard Ficoll density-gradient centrifugation
Based on one decade’s studying accumulation, we are the first to present the downregulation of miR-155 in PBMCs from Lumbar disc degeneration (LDD) patients, implicating the immune interaction between PBMCs and NP cells in LDD via miR-155

Summary

Introduction

As the chief cells in nucleus pulposus (NP) tissues, NP cells contribute significantly to the development of intervertebral disc degeneration (IDD), which is the leading cause of low back pain (Richardson et al, 2017). The disc degeneration process depends on the state of NP cells by affecting the extracellular matrix (ECM), intercellular interaction, gene regulation, inflammation, and auto-immunity (Banala et al, 2018). These mechanisms result in the morphologic changes of NP cells and pertaining ECM alterations, leading to disc degeneration in clinical and radiological manifestation. The disc degeneration process goes with cell death (Zhang et al, 2016). Regulated active necrosis has expanded to a number of forms, including necroptosis

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