Melatonin Prevents Chondrocyte Matrix Degradation in Rats with Experimentally Induced Osteoarthritis by Inhibiting Nuclear Factor-κB via SIRT1

Zhao, Mingchao; Song, Xiaopeng; Chen, Hong; Ma, Tianwen; Tang, Jilang; Wang, Xinyu; Yu, Yue; Lv, Liangqiu; Jia, Litao; Li, Gao

doi:10.3390/nu14193966

Cited by 17 publications

(8 citation statements)

References 65 publications

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“…The treatment with IL-1β induced upregulation of MMP-3, MMP-9, MMP-13, ADAMTS-4, COX-2 and iNOS levels, while downregulation of chondrogenic marker COL2A1 in human mesenchymal stem cells (hMSCs) and chondrocytes. However, melatonin significantly mitigated the detrimental effects caused by IL-1β ( 154 , 155 , 158 ). By inhibiting the JAK2/STAT3 signaling pathway, melatonin effectively reduced the levels of MMP-3, MMP-9, and MMP-13, thereby attenuating cartilage degradation ( 138 ) ( Figure 3 ).…”

Section: Melatonin Targeting Oxidative Stress Inflammation and Chondr...mentioning

confidence: 96%

“…Zhao et al. likewise testified that melatonin downregulates IL-1β-induced phosphorylation levels of P65 and IκBα in chondrocytes via SIRT1 pathways, thus abolishing NF-κB activation to function in cytoprotective and anti-inflammatory effects ( 155 ). It has been demonstrated that the toll-like receptor (TLR) mediates inflammatory responses triggered by chemical and physical stressors, such as cytokines and mechanical damage, ultimately leading to the development of OA ( 163 ).…”

Section: Melatonin Targeting Oxidative Stress Inflammation and Chondr...mentioning

confidence: 99%

“…Several studies have shown that the synthesis of ECM and the differentiation, migration, and adhesion of chondrocytes were all significantly influenced by TGF-β1 ( 169 , 170 ). Activation of the TGF-β1/Smad2 pathway stimulated by melatonin in IL-1β-induced chondrocytes was found contributing to the synthesis of ECM ( 155 ). It was suggested that melatonin administration in chondrocytes increased the upregulation of key chondrogenic marker genes, including Sox9, aggrecan, and collagen II via the TGF-β1 signaling pathway ( 171 ).…”

Section: Melatonin Targeting Oxidative Stress Inflammation and Chondr...mentioning

confidence: 99%

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Therapeutic targets and potential delivery systems of melatonin in osteoarthritis

Xiong,

Peng,

Deng

et al. 2024

Front. Immunol.

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Osteoarthritis (OA) is a highly prevalent age-related musculoskeletal disorder that typically results in chronic pain and disability. OA is a multifactorial disease, with increased oxidative stress, dysregulated inflammatory response, and impaired matrix metabolism contributing to its onset and progression. The neurohormone melatonin, primarily synthesized by the pineal gland, has emerged as a promising therapeutic agent for OA due to its potential to alleviate inflammation, oxidative stress, and chondrocyte death with minimal adverse effects. The present review provides a comprehensive summary of the current understanding regarding melatonin as a promising pharmaceutical agent for the treatment of OA, along with an exploration of various delivery systems that can be utilized for melatonin administration. These findings may provide novel therapeutic strategies and targets for inhibiting the advancement of OA.

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Section: Melatonin Targeting Oxidative Stress Inflammation and Chondr...mentioning

confidence: 96%

Section: Melatonin Targeting Oxidative Stress Inflammation and Chondr...mentioning

confidence: 99%

Section: Melatonin Targeting Oxidative Stress Inflammation and Chondr...mentioning

confidence: 99%

See 1 more Smart Citation

Therapeutic targets and potential delivery systems of melatonin in osteoarthritis

Xiong,

Peng,

Deng

et al. 2024

Front. Immunol.

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“…SIRT1, a nicotinamide adenine dinucleotide (NAD)-dependent nuclear histone deacetylase, has been reported to downregulate the activity of NF-κB in rat chondrocytes ( 54 ). SIRT1 promotes the deacetylation of p65 and suppresses the nuclear translocation of NF-κB, protecting against the inflammatory responses in articular chondrocytes and the development of OA ( 55 ).…”

Section: Nf-κb Signaling In the Physiology And Pathogenesis Of Chondr...mentioning

confidence: 99%

The protective activity of natural flavonoids against osteoarthritis by targeting NF-κB signaling pathway

Zhou

2023

Front. Endocrinol.

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Osteoarthritis (OA) is a typical joint disease associated with chronic inflammation. The nuclear factor-kappaB (NF-κB) pathway plays an important role in inflammatory activity and inhibiting NF-κB-mediated inflammation can be a potential strategy for treating OA. Flavonoids are a class of naturally occurring polyphenols with anti-inflammatory properties. Structurally, natural flavonoids can be divided into several sub-groups, including flavonols, flavones, flavanols/catechins, flavanones, anthocyanins, and isoflavones. Increasing evidence demonstrates that natural flavonoids exhibit protective activity against the pathological changes of OA by inhibiting the NF-κB signaling pathway. Potentially, natural flavonoids may suppress NF-κB signaling-mediated inflammatory responses, ECM degradation, and chondrocyte apoptosis. The different biological actions of natural flavonoids against the NF-κB signaling pathway in OA chondrocytes might be associated with the differentially substituted groups on the structures. In this review, the efficacy and action mechanism of natural flavonoids against the development of OA are discussed by targeting the NF-κB signaling pathway. Potentially, flavonoids could become useful inhibitors of the NF-κB signaling pathway for the therapeutic management of OA.

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“…Moreover, dysfunction of mitochondria has also been reported in the occurrence of OA diseases 7,15 . Some small molecules such as Urolithin A and melatonin have been shown to reduce cartilage damage and restore cartilage function in the progress of OA by improving mitochondrial function in chondrocytes 16,17 . Therefore, exploring the influence mechanisms of mitochondrial morphology and function changes in chondrocytes is conducive to the studies of new treatments for OA.…”

Section: Introductionmentioning

confidence: 99%

TGF‐β3 mediates mitochondrial dynamics through the p‐Smad3/AMPK pathway

Du,

Duan,

Kan

et al. 2023

Cell Proliferation

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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.

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Melatonin Prevents Chondrocyte Matrix Degradation in Rats with Experimentally Induced Osteoarthritis by Inhibiting Nuclear Factor-κB via SIRT1

Cited by 17 publications

References 65 publications

Therapeutic targets and potential delivery systems of melatonin in osteoarthritis

Therapeutic targets and potential delivery systems of melatonin in osteoarthritis

The protective activity of natural flavonoids against osteoarthritis by targeting NF-κB signaling pathway

TGF‐β3 mediates mitochondrial dynamics through the p‐Smad3/AMPK pathway

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