From disease model to therapeutic insight: An engineered hydrogel reveals the role of matrix viscous dissipation in intervertebral disc degeneration - PubMed
5 hours ago
- #Mechanotransduction
- #Cellular senescence
- #Intervertebral disc degeneration
- Intervertebral disc degeneration (IVDD) is a major cause of low back pain.
- Reduced nucleus pulposus (NP) viscous dissipation correlates with IVDD severity in clinical specimens and rat models.
- Engineered hydrogels mimicking healthy and degenerated NP properties show decreased viscous dissipation induces NP cell (NPC) senescence via YAP suppression.
- NPCs sense ECM viscous dissipation changes through ITGB1, affecting cell adhesion and YAP activity.
- Reduced viscous dissipation leads to nuclear envelope integrity loss and cytosolic DNA accumulation, activating the cGAS-STING pathway and NPC senescence.
- NPC senescence alters ECM components, potentially creating a vicious cycle of further viscous dissipation reduction.
- Pharmacological YAP activation and biomimetic hydrogel implantation alleviate the cycle and suppress IVDD progression in vivo.