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

[摘要] 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 localextracellular space in IDD. The study aimed for investigating the miR-155 expression of PBMCs, extracellularmiRNAs (ex-miRNAs) of human nucleus pulposus (NP) tissues, and morphological changes of cell death in the IDDprocess. Here, we harvested peripheral blood and NP samples from scoliosis and IDD patients as control anddegenerative 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 inPBMCs. 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 inmonocytes/macrophages. Moreover, we identified 594 shared hsa-miRNAs as the intracellular miRNA expressionprofile and 258 miRNAs as the ex-miRNA expression profile in human NP tissue. miR-155 was amongst intracellularmiRNAs in NP. TEM observation presented multiple endocytic secretory vesicles within human NP cells, implicatingexosome transporting machinery. Typical necroptosis and pyroptosis were noted in human NP. Collectively, thisstudy reveals miR-155 expression in PBMCs from IDD patients. Moreover, we propose ex-miRNA expression profileand necroptosis/pyroptosis in human NP tissue, shedding novel light on the etiology of IDD.

[学科分类] 仪器

[关键词] miR-155;PBMCs;Lumbar disc disease;Auto-immunity;Cell death;Exosome