Hybrid extracellular vesicles drive irreversible mitochondria damage and TCA metabolite deficiency-related chondrocyte senescence - PubMed
3 hours ago
- #mitochondrial dysfunction
- #extracellular vesicles
- #osteoarthritis
- Identified a subtype of hybrid extracellular vesicles (hEVs) enriched in OA joint fluid, correlating with severity.
- hEVs carry dual markers from macrophages and chondrocytes, promoting uptake and metabolic regulation.
- hEVs cause irreversible mitochondrial fragmentation and cellular aging in OA chondrocytes, unlike reversible inflammation effects.
- Mechanism involves ADT1-dependent decrease in mitochondrial membrane potential and depletion of TCA metabolites like acetyl-CoA and α-KG.
- Combination therapy with ADT1 inhibitor plus acetyl-CoA and α-KG restored metabolic function and reduced aging in OA models.