cGAS-STING/HMGB1-mediated senescence induced by LRRK2 accelerates cartilage degeneration in osteoarthritis - PubMed
5 hours ago
- #mitochondrial dysfunction
- #cellular senescence
- #osteoarthritis
- Mitochondrial dysfunction-driven senescence is a key mechanism in osteoarthritis (OA) development.
- LRRK2, a multifunctional kinase, is implicated in mitochondrial homeostasis and inflammatory conditions.
- LRRK2 overexpression accelerates chondrocyte senescence and worsens cartilage degeneration in OA.
- LRRK2 promotes HMGB1 upregulation by modulating GTPase activity, aggravating chondrocyte senescence.
- LRRK2 activates the cGAS-STING signaling pathway, increasing HMGB1 expression and mitochondrial dysfunction.
- STING inhibitor H-151 partially mitigates LRRK2-induced chondrocyte senescence and mitochondrial impairment.
- LRRK2 drives chondrocyte senescence via the cGAS-STING-HMGB1 axis, suggesting a therapeutic target for OA.