Rescuing ACE2-Deficiency-Mediated Nucleus Pulposus Senescence and Intervertebral Disc Degeneration by a Nanotopology-Enhanced RNAi System.

ABSTRACT: Nucleus pulposus cell (NPC) senescence contributes to intervertebral disc degeneration (IVDD). However, the underlying molecular mechanisms are not fully understood. In this study, it is demonstrated that angiotensin-converting enzyme 2 (ACE2) counteracted the aging of NPCs and IVDD at the cellular and physiological levels. The expression of ACE2 correlates negatively with the degree of NPC senescence and IVDD. Using both loss- and gain-of-function mouse models, it is revealed that ACE2 deficiency increased the senescence of NPCs and exacerbated injury- or instability-induced IVDD, whereas ACE2 overexpression counteracted these detrimental effects. Mechanistically, integrated analysis of single-cell and bulk transcriptomics shows that ACE2 deficiency results in the activation of TGFβ2/Smad

SUBMITTER: Sun K 

PROVIDER: S-EPMC11884558 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature