Reprogramming to restore youthful epigenetics of senescent nucleus pulposus cells for mitigating intervertebral disc degeneration and alleviating low back pain.

ABSTRACT: Aging is a pivotal risk factor for intervertebral disc degeneration (IVDD) and chronic low back pain (LBP). The restoration of aging nucleus pulposus cells (NPCs) to a youthful epigenetic state is crucial for IVDD treatment, but remains a formidable challenge. Here, we proposed a strategy to partially reprogram and reinstate youthful epigenetics of senescent NPCs by delivering a plasmid carrier that expressed pluripotency-associated genes (Oct4, Klf4 and Sox2) in Cavin2-modified exosomes (OKS@M-Exo) for treatment of IVDD and alleviating LBP. The functional OKS@M-Exo efficaciously alleviated senescence markers (p16^INK4a, p21^CIP1 and p53), reduced DNA damage and H4K20me3 expression, as well as restored proliferation ability and metabolic balance in senescent NPCs, as va

SUBMITTER: Ma W 

PROVIDER: S-EPMC11903667 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature