PRDM1 expression was substantially upregulated in degenerated nucleus pulposus tissues and cells.
PRDM1 is linked to the regulation of cell death and inflammatory responses.
Overexpression of PRDM1 promotes in nucleus pulposus cells, worsening intervertebral disc degeneration.
Silencing PRDM1 reduces pyroptosis in these cells and may slow degeneration.
PRDM1 activates the transcription of CASP1, contributing to the pyroptotic process.
Inhibition of CASP1 can counteract the effects of PRDM1 on cell death.
Simplified
Intervertebral disc degeneration (IVDD) is a primary contributor to low back pain and poses a considerable burden to society. However, the molecular mechanisms underlying IVDD remain to be elucidated. PR/SET domain 1 (PRDM1) regulates cell proliferation, apoptosis, and inflammatory responses in various diseases. Despite these regulatory functions, the mechanism of action of PRDM1 in IVDD remains unexplored. In this study, we investigated the role and underlying mechanisms of action of PRDM1 in IVDD progression. The expression of PRDM1 in nucleus pulposus (NP) tissues and NP cells (NPCs) was assessed using western blotting, immunohistochemistry, and immunofluorescence. The effects of PRDM1 on IVDD progression were investigated in vitro and in vivo. Mechanistically, mRNA sequencing, chromatin immunoprecipitation, and dual-luciferase reporter assays were performed to confirm that PRDM1 triggered CASP1 transcription. Our study demonstrated for the first time that PRDM1 expression was substantially upregulated in degenerated NP tissues and NPCs. PRDM1 overexpression promoted NPCs by inhibiting and exacerbating IVDD progression, whereas PRDM1 silencing exerted the opposite effect. Furthermore, PRDM1 activated CASP1 transcription, thereby promoting NPCs pyroptosis in vitro. Notably, CASP1 silencing reversed the effects of PRDM1 on the NPCs. To the best of our knowledge, this study is the first to demonstrate that PRDM1 silencing inhibits NPCs pyroptosis by repressing CASP1 transcription, which may be a promising new therapeutic target for IVDD.
Key numbers
substantially upregulated
Increase in PRDM1 expression
Observed in degenerated NP tissues and NPCs
substantially inhibited
NPC proliferation inhibition
PRDM1 overexpression effects on NPCs
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