Tgf-Β3 Mediates Mitochondrial Dynamics Through P-Smad3/Ampk Pathway

Cartilage is an important component of the temporomandibular joint.It is well recognized that mitochondrial dynamics plays a vital role in cartilage physiology. Any perturbation in mitochondrial dynamics could cause disorders in cartilage metabolism and even lead to the occurrence of cartilage diseases such as osteoarthritis (OA). TGF-β3, as an important growth factor that appears in the joints of OA disease, shows its great potential in chondrocyte growth and metabolism. Nevertheless, the role of TGF-β3 on mitochondrial dynamics is still not well understood. Here we aimed to investigate the effect of TGF-β3 on mitochondrial dynamics of chondrocytes and reveal its underlying bio-mechanism.This will provide new ideas for the treatment of temporomandibular joint disorders. Transmission electron microscopy (TEM) was employed to detect the number and morphology of mitochondria. Western blotting was conducted to detect the protein expressions. Immunofluorescence was performed to detect the cytoplasmic distributions of proteins. RNA sequencing was to detect the transcriptome changes related to mitochondrial dynamics. TGF-β3 could increase the number of mitochondria in chondrocytes. TGF-β3-enhanced mitochondrial number was via promoting the mitochondrial fission. The mitochondrial fission induced by TGF-β3 was mediated by AMPK signaling. TGF-β3 activated canonical p-Smad3 signaling and resultantly mediated AMPK-induced mitochondrial fission. These results elucidate an understanding of the role of TGF-β3 on mitochondrial dynamics in chondrocytes and provide potential cues for therapeutic strategies in temporomandibular joint cartilage injury and OA disease in terms of energy metabolism.