BioAcyl Corp
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Li, K., Yang, T., & Chen, F. (2025). MOTS-c attenuates mitochondrial dysfunction induces pyroptosis and cartilage degradation in osteoarthritis via an Nrf2-Dependent Mechanism. Free Radical Biology and Medicine, 241, 717–731. Added by: Dr. Enrique Feoli (22/03/2026, 16:18) Last edited by: Dr. Enrique Feoli (22/03/2026, 16:21) |
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| Resource type: Journal Article DOI: 10.1016/j.freeradbiomed.2025.09.056 ID no. (ISBN etc.): 0891-5849 BibTeX citation key: Li2025 View all bibliographic details  |
Categories: BioAcyl Corp Subcategories: MOTS.c Keywords: Mitochondrial function, MOTS-c, NLRP3, NRF2, Osteoarthritis, Pyroptosis Creators: Chen, Li, Yang Collection: Free Radical Biology and Medicine |
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| Abstract |
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Osteoarthritis, a common chronic degenerative disease in the field of orthopedics, is caused by the interaction of mechanical stress, traumatic inflammation, and metabolic imbalance, and this interaction progresses over time. MOTS-c, a mitochondria-derived peptide, exerts pivotal roles in regulating metabolism, anti-inflammation, and antioxidant stress responses. However, current research on the role of MOTS-c in osteoarthritis remains scarce, and its specific mechanism of action remains unclear. Therefore, this study aims to further explore the molecular mechanisms by which MOTS-c regulates osteoarthritis. Exogenous supplementation of MOTS-c improves mitochondrial dysfunction, inhibits the activation of inflammatory bodies and rescues chondrocyte pyroptosis, thereby regulating the metabolic balance of extracellular matrix (ECM). Mechanistically, MOTS-c plays a key role in LPS-induced oxidative stress and chondrocyte pyroptosis through the Nrf2/TXNIP/NLRP3 axis. Our research demonstrates that MOTS-c can not only effectively inhibit the expression of inflammatory factors but also promote the expression of major components of the extracellular matrix (ECM) and suppress the production of matrix metalloproteinases. We validated the in vivo efficacy of MOTS-c by establishing a murine osteoarthritis model. Analysis of imaging and histopathological results revealed that MOTS-c can effectively delay the degeneration of articular cartilage and ameliorate the progression of osteoarthritis. Collectively, our findings uncover the intrinsic regulatory mechanism of MOTS-c in chondrocytes and its potential value in the treatment of osteoarthritis.
Added by: Dr. Enrique Feoli Last edited by: Dr. Enrique Feoli |
| Notes |
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MOTS-c is a mitochondria-derived peptide encoded within the mitochondrial genome's 12S rRNA. In recent years, it has been recognized as a key regulator involved in mitochondrial retrograde signaling [18]. Studies have demonstrated that this peptide can translocate into the nucleus, enhance mitochondrial homeostasis by increasing mitochondrial membrane potential through reducing oxygen consumption and reactive oxygen species (ROS) production [19,20]. A growing body of research has elucidated that MOTS-c can prevent obesity, diabetes, osteoporosis, and aging by ameliorating mitochondrial function [[20], [21], [22], [23]]. Beyond these roles, MOTS-c also exerts a pivotal influence on multiple cellular regulatory processes, including the modulation of cell death, inflammation, and oxidative stress [24]. Previous studies have documented that MOTS-c possesses potent anti-inflammatory properties, as evidenced by its therapeutic efficacy in treating sepsis induced by methicillin-resistant Staphylococcus aureus, lipopolysaccharide (LPS)-triggered acute lung injury, and dextran sulfate sodium-induced colitis [25,26]. Upon exposure to stress stimuli, MOTS-c regulates the expression of a large number of genes and interacts with stress response transcription factors (such as nuclear factor erythroblast 2 related factor 2/NRF2), exerting critical functions through regulating retrograde signaling that influences nuclear gene expression and maintaining intracellular homeostasis [27].
Added by: Dr. Enrique Feoli Last edited by: Dr. Enrique Feoli |