PRDX6 attenuates osteoporotic bone loss by restraining oxidative stress-associated osteoblast senescence - PubMed
3 hours ago
- #Osteoporosis
- #Senescence
- #Oxidative Stress
- PRDX6 levels are reduced in ovariectomized (OVX) mice and correlate with osteoporotic bone loss.
- In MC3T3-E1 cells, PRDX6 knockdown increases ROS accumulation, enhances senescence, and impairs osteogenic function, while overexpression has protective effects.
- PRDX6 knockdown promotes osteoclast differentiation in RAW264.7 cells and BMMs, with a paracrine contribution observed in osteoblast-osteoclast co-culture.
- RNA-seq analysis identifies cAMP pathways, with PRDX6 modulation affecting intracellular cAMP levels and PKA/CREB phosphorylation.
- Genetic and pharmacological interventions show that cAMP/PKA/CREB signaling is functionally required for PRDX6-dependent osteogenic maintenance.
- Mutant-rescue experiments reveal that the peroxidase activity (via PRDX6-WT) is critical for restoring cAMP signaling and osteogenic function, while the aiPLA2 activity is less essential.