SIRT3 and osteoarthritis: Previous studies have demonstrated that reprogramming the SIRT3-COX4I2 axis can reduce the progression of osteoarthritis.[45] Studies have revealed that hypoxia-inducible factor-1 controls the expression of COX4 subunits by triggering the transcription of COX4I2, thus manipulating the activity of the COX family, ATP synthesis, and reactive oxygen species generation.