USP5-Rich Apoptotic Extracellular Vesicles Regulate Nucleus Pulposus Cells Apoptosis and DNA Damage Repair by Preventing E2F1 Proteasomal Degradation.

ABSTRACT: Mesenchymal stem cell (MSC) transplantation is considered one of the most promising regenerative strategies for treating degenerative musculoskeletal diseases, yet its underlying therapeutic mechanisms remain incompletely understood. In this study, we demonstrate that transplanted MSCs regulate apoptosis and DNA damage repair (DDR) in senescent nucleus pulposus cells (NPCs) by releasing apoptotic extracellular vesicles (ApoEVs), thereby delaying the process of intervertebral disc degeneration (IVDD). Mechanistically, we found that NPCs in degenerated discs exhibit abnormal subcellular localization of the deubiquitinase ubiquitin specific peptidase 5 (USP5), with excessive cytoplasmic retention leading to aberrant ubiquitination and degradation of the E2F transcription factor 1 (E2F1). Foll

SUBMITTER: Shi P 

PROVIDER: S-EPMC12365387 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature