Region-dependent expression and function of integrin α5β1 in protecting against disc degeneration via autophagy promotion: an ex vivo organ culture model under dynamic mechanical loading - PubMed
7 hours ago
- #intervertebral disc degeneration
- #integrin α5β1
- #autophagy
- The study investigates the role of integrin α5β1 in protecting against intervertebral disc degeneration (IVDD) by promoting autophagy under dynamic mechanical loading.
- Bovine intervertebral discs were subjected to physiological and degenerative loading, with interventions including autophagy inhibitor 3-MA, integrin α5β1 inhibitor RGD, and autophagy activator rapamycin.
- Degenerative loading led to IVDD, characterized by disc height loss, structural disruption, decreased cell viability, and ECM metabolic imbalance, exacerbated by 3-MA.
- Integrin α5β1 showed region-specific upregulation in the nucleus pulposus and inner annulus fibrosus under degenerative loading, while only β1 subunit increased in the outer annulus fibrosus.
- RGD peptide inhibition of integrin α5β1 suppressed autophagy, increased apoptosis, and promoted ECM degradation, whereas rapamycin alleviated degeneration by restoring autophagy.
- Mechanistically, degenerative loading suppressed the FAK/PI3K/AKT/mTOR pathway and upregulated ULK1, effects partially reversed by RGD inhibition.
- The study suggests targeting the integrin-autophagy axis and associated pathways as a potential therapeutic strategy for mechanically induced IVDD.