CaMKII Activation Enhances Antioxidant Defence and Mitochondrial Function in human articular chondrocytes
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Background
The articular cartilage has limited vascular supply and repair capacity, making it particularly susceptible to reactive oxygen species (ROS)-driven oxidative damage. Excess ROS contributes to extracellular matrix breakdown and is a major factor in osteoarthritis (OA) progression. We previously identified Calcium/Calmodulin-dependent protein kinase II (CaMKII) as a regulator of cartilage homeostasis, prompting us to investigate its role during oxidative stress.
Methods
Primary adult human articular chondrocytes were isolated from OA cartilage. CaMKII activity was modulated using adenoviral overexpression of a constitutively active form of the kinase or of Autocamtide-2–related inhibitory peptide, a CaMKII inhibitor. Redox status and mitochondrial function were assessed by molecular and metabolic assays.
Results
Oxidative stress increased CaMKII phosphorylation. CaMKII inhibition elevated cellular and mitochondrial ROS, whereas CaMKII activation enhanced mitochondrial respiration capacity, improved mitochondrial morphology, and was associated to NRF2 nuclear translocation.
Conclusion
CaMKII supports redox homeostasis in chondrocytes and may represent a therapeutic strategy to preserve cartilage integrity and delay disease onset.
