The long non‐coding RNA maternally expressed 3‐micorRNA‐15a‐5p axis is modulated by melatonin and prevents nucleus pulposus cell inflammation and apoptosis

Abstract

Nucleus pulposus (NP) cell apoptosis is regarded as a critical risk factor for intervertebral disc degeneration (IVDD). Melatonin exerts a protective role on NP cells. The study concentrates on the role and mechanism of lncRNA MEG3 in melatonin‐mediated effects on NP cells. An in‐vitro IVDD model was constructed using IL‐1β on human NP cells. qRT‐PCR investigated MEG3, miR‐15a‐5p, and PGC‐1α mRNA levels in tissues and NP cells. IL‐1β treated NP cells subsequent to transfection, followed by melatonin treatment. NP cell proliferation, viability, apoptosis, and inflammatory reactions were assayed. Western blot checked the profiles of PGC‐1α, SIRT1, and NF‐κB p65. Student t‐test or one‐way analysis of variance (ANOVA) followed by Tukey's test were used for statistical tests. As indicated by the data, melatonin weakened NP cell inflammation and apoptosis and enhanced MEG3 expression. MEG3 expression was attenuated in IVDD tissues. MEG3 knockdown impaired the function of melatonin, which was, however, strengthened by miR‐15a‐5p knockdown. MEG3 targeted miR‐15a‐5p, which targeted PGC‐1α and repressed the PGC‐1α/SIRT1 pathway. Collectively, this study has disclosed that the MEG3‐miR‐15a‐5p‐PGC‐1α/SIRT1 pathway modulated by melatonin can hamper nucleus pulposus cell apoptosis and inflammation elicited by IL‐1β.

Analysis of global research hotspots and trends in immune cells in intervertebral disc degeneration: A bibliometric study

“… 76 Another study also revealed that melatonin impedes NPCs apoptosis and IL-1β-induced inflammation by regulating the MEG3-miR-15a-5p-PGC-1α/SIRT1 pathway. 77 The above results suggest that immune cells, cell death, senescence, changes in mRNA, inflammatory responses, and ECM degradation all contribute to the development of IDD, and that they often do not exist independently, but rather interact with each other and work together. Due to the specificity of the disc structure, more work needs to be done in later studies to improve precise immune control.…”

Research progress on long non‑coding RNAs in non‑infectious spinal diseases (Review)

“…Subsequent overexpression experiments demonstrated the impact of the HCG18/miR-495-3p/FSTL1 signalling axis on NP tissue inflammation and apoptosis ( 85 ). Zhang et al ( 86 ) showed that melatonin can reduce inflammation and apoptosis in NP cells while upregulating maternally expressed gene 3 (MEG3) expression, whereas MEG3 expression was shown to be downregulated in the degenerated NP. The study revealed that melatonin can reduce NP cell inflammation and apoptosis through the MEG3/miR-15a-5p/peroxisome proliferator-activated receptor γ coactivator 1α/SIRT1 pathway.…”