PRDM1 promotes nucleus pulposus cell pyroptosis leading to intervertebral disc degeneration via activating CASP1 transcription

• DOI: 10.1007/s10565-024-09932-y
• Publication Date: 2024-10-21T08:02:51Z
• Authors: Cheng Yu; Jianjun Li; Wenhao Kuang; Songjia Ni; Yanlin Cao; Yang Duan
• Keywords: Degeneration (medical); Intervertebral Disc; Pyroptosis; Transcription

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