Traditional Chinese medicine-derived monomers delay osteoarthritis progression by regulating mitochondrial homeostasis.

Osteoarthritis is a common degenerative disease characterized by the degeneration of articular cartilage, which also affects the synovium, subchondral bone, and the joint microenvironment. Currently, clinical treatment remains focused primarily on pain relief and symptom improvement, with a lack of disease-modifying strategies capable of effectively slowing disease progression. In recent years, the role of mitochondrial homeostasis imbalance in the pathogenesis and progression of osteoarthritis has gradually gained attention. Mitochondria not only participate in the energy supply of chondrocytes but are also closely associated with oxidative stress, mitochondrial dynamics, mitochondrial autophagy, apoptosis, cellular senescence, and extracellular matrix metabolism. In the osteoarthritis microenvironment, inflammatory stimuli, abnormal mechanical loading, and age-related stress disrupt mitochondrial function, leading to reactive oxygen species accumulation, membrane potential decline, and impaired energy metabolism, which in turn promote chondrocyte dysfunction and joint degeneration. A growing body of research indicates that single compounds derived from traditional Chinese medicine can exert protective effects by regulating mitochondrial homeostasis, thereby alleviating oxidative stress, improving energy metabolism, maintaining mitochondrial function, promoting moderate mitochondrial autophagy, and inhibiting chondrocyte apoptosis and senescence. Ultimately, these actions reduce inflammatory responses and matrix degradation, thereby delaying the progression of osteoarthritis. This article reviews the pathological role of mitochondrial homeostasis imbalance in osteoarthritis, summarizes recent research progress on TCM-derived monomers, and outlines current challenges and future directions.