Self-amplifying loop of NF-κB and periostin initiated by PIEZO1 accelerates mechano-induced senescence of nucleus pulposus cells and intervertebral disc degeneration.

ABSTRACT: Abnormal mechanical load is a main risk factor of intervertebral disc degeneration (IDD), and cellular senescence is a pathological change in IDD. In addition, extracellular matrix (ECM) stiffness promotes human nucleus pulposus cells (hNPCs) senescence. However, the molecular mechanism underlying mechano-induced cellular senescence and IDD progression is not yet fully elucidated. First, we demonstrated that mechano-stress promoted hNPCs senescence via NF-κB signaling. Subsequently, we identified periostin as the main mechano-responsive molecule in hNPCs through unbiased sequencing, which was transcriptionally upregulated by NF-κB p65; moreover, secreted periostin by senescent hNPCs further promoted senescence and upregulated the catabolic process in hNPCs through activating NF-κB, forming

SUBMITTER: Wu J 

PROVIDER: S-EPMC9552911 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature