Abstract: BACKGROUND: During the pathogenesis of osteoarthritis, chondrocytes exhibit insufficient energy supply. As mitochondria serve as the energy generators of cells, it remains unclear how changes in mitochondrial dynamic homeostasis affect chondrocyte function and cartilage degeneration.
OBJECTIVE: To investigate the effect of mitochondrial dynamics homeostasis in articular chondrocytes on cartilage degeneration in knee osteoarthritis.
METHODS: (1) Sprague-Dawley rats were randomly divided into a control group and a model group. The model group underwent anterior cruciate ligament transection to establish a rat model of knee osteoarthritis, and all rats were normally fed for 4 weeks. Articular cartilage changes were observed using hematoxylin-eosin and safranin O-fast green staining. The protein and mRNA expression levels of optic atrophy 1 and dynamin-related protein 1 in cartilage, as well as mitochondrial DNA expression, were detected using immunohistochemistry, immunofluorescence, western blot, and RT-PCR. Adenosine triphosphate expression was measured using an ATP colorimetric assay. (2) Additionally, 10 tibial plateau cartilage samples were collected. Five samples from patients without osteoarthritis undergoing amputation or trauma surgery served as the normal group, and five samples from patients with knee osteoarthritis undergoing knee replacement surgery served as the lesion group. Western blot and RT-PCR were used to examine the above indicators, along with the expression of mitofusin 1 and mitochondrial fission protein 1.
RESULTS AND CONCLUSION: (1) Cartilage observation indicators in rat models: Compared with the control group, the model group showed thinning of the cartilage layer, destruction of subchondral bone structure, disorganized chondrocyte arrangement, and reduced cell number. The levels of the mitochondrial fusion protein (optic atrophy 1) and its mRNA expression, as well as mitochondrial DNA expression, were decreased in chondrocytes, while the levels of the mitochondrial fission protein (dynamin-related protein 1) and its mRNA expression were increased, and adenosine triphosphate content was decreased. (2) Human tibial plateau cartilage observation indicators: Compared with the normal group, the lesion group showed decreased protein expression of mitochondrial fusion proteins (optic atrophy 1 and mitofusin 1) and their mRNA expression, as well as decreased mitochondrial DNA expression, while the protein expression of mitochondrial fission proteins (dynamin-related protein 1 and mitochondrial fission protein 1) and their mRNA expression were increased, and adenosine triphosphate content was decreased. In conclusion, the imbalance of mitochondrial dynamics homeostasis in articular chondrocytes is manifested by downregulation of mitochondrial fusion protein expression, upregulation of fission protein expression, and impaired adenosine triphosphate synthesis, which is significantly positively correlated with cartilage damage.

Key words: mitochondrial dynamics, articular cartilage, osteoarthritis, mitochondrial fission, mitochondrial fusion