TGF-β3 mediates mitochondrial dynamics through the p-Smad3/AMPK pathway
Received date: 06 Sep 2023
Revised date: 06 Nov 2023
Accepted date: 07 Nov 2023
Copyright
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. By using transmission electron microscopy (TEM) for the number and morphology of mitochondria, western blotting for the protein expressions, immunofluorescence for the cytoplasmic distributions of proteins, and RNA sequencing for the transcriptome changes related to mitochondrial dynamics. We found that 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. Taken together, these results elucidate an understanding of the role of TGF-β3 on mitochondrial dynamics in chondrocytes and provide potential cues for therapeutic strategies in cartilage injury and OA disease in terms of energy metabolism.
Xinmei Du , Mengmeng Duan , Shiyi Kan , Yueyi Yang , Siqun Xu , Jieya Wei , Jiazhou Li , Hao Chen , Xuedong Zhou , Jing Xie . TGF-β3 mediates mitochondrial dynamics through the p-Smad3/AMPK pathway[J]. Cell Proliferation, 2024 , 57(5) : e13579 . DOI: 10.1111/cpr.13579
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