Dimeric PKM2 in chondrocytes impairs mitochondrial homeostasis in osteoarthritis - PubMed
3 hours ago
- #PKM2 Dimerization
- #Mitochondrial Homeostasis
- #Osteoarthritis
- PKM2 dimerization is increased in both human and murine osteoarthritic cartilage, linked to extracellular matrix (ECM) degradation in osteoarthritis (OA).
- PKM2 deficiency or tetramer stabilization with TEPP-46 reduces OA progression, enhances cartilage matrix production, and preserves mitochondrial function via disruption of PKM2-ERK interaction.
- The protective effects involve ERK-dependent upregulation of mitochondrial fusion protein MFN1 (but not MFN2); MFN1 knockdown reverses chondroprotection from PKM2 deficiency.
- Targeting PKM2 dimerization may offer a therapeutic strategy for OA by improving mitochondrial homeostasis and ECM integrity.
- Study protocols were ethically approved for human and animal samples, with no competing interests declared.