METTL3 involves the progression of osteoarthritis probably by affecting ECM degradation and regulating the inflammatory response

Sang, Weilin; Xue, Song; Jiang, Yafei; Lu, Haiming; Zhu, Libo; Wang, Cong; Ma, Jinzhong

doi:10.1016/j.lfs.2021.119528

Cited by 45 publications

(47 citation statements)

References 30 publications

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“…Several studies have shown that METTL3 promotes the inflammatory response by weakening the malabsorptive activity of LCFAs in vitro ( 31 ). In addition, knocking down METTL3 inhibits the IL-1β-induced inflammatory response and extracellular matrix (ECM) synthesis ( 32 , 33 ). In contrast, METTL3 knockdown inhibits osteoblast differentiation and Smad-dependent signaling and activated the inflammatory response by regulating MAPK signaling in LPS-induced inflammation ( 34 ).…”

Section: Discussionmentioning

confidence: 99%

METTL3-Mediated N6-Methyladenosine Modification of Trim59 mRNA Protects Against Sepsis-Induced Acute Respiratory Distress Syndrome

Chen

Zhu

et al. 2022

Front. Immunol.

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N6-methyladenosine (m6A) RNA modification is a fundamental determinant of mRNA metabolism in eukaryotic cells and is involved in numerous physiological and pathological processes. However, the specific role of m6A modification in sepsis-induced acute respiratory distress syndrome(ARDS) remains unknown. Here, we show that the levels of m6A RNA were significantly decreased in septic lungs and that METTL3 was the main regulator involved in the absence of m6A RNA modification. Pulmonary endothelial barrier damage is a critical process in the pathogenesis of acute lung injury during sepsis. METTL3 regulated endothelial barrier dysfunction and inflammatory responses in sepsis-induced ARDS in vivo and in vitro. Furthermore, we identified tripartite motif-containing (Trim)59 as a key m6A effector and Trim59 deficiency exacerbated lung injury. Mechanistically, METTL3 inhibited endothelial injury in sepsis-induced ARDS through Trim59-associated NF-κB inactivation. Our findings revealed novel insights into epitranscriptional mechanisms in sepsis-induced ARDS via m6A modifications, which has important application value in the diagnosis, prognosis, and molecular-targeted therapy of sepsis-associated lung injury.

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Section: Discussionmentioning

confidence: 99%

METTL3-Mediated N6-Methyladenosine Modification of Trim59 mRNA Protects Against Sepsis-Induced Acute Respiratory Distress Syndrome

Chen

Zhu

et al. 2022

Front. Immunol.

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“…M 6 A modification broadly distributes in diverse pathophysiological process, which is installed by ‘writers’ refer to the RNA methyltransferases, including methyltransferase-like 3 (METTL3), methyltransferase-like 14 (METTL14), Wilms Tumor 1-associated protein (WTAP), RNA-binding motif 15 (RBM15) [ 11 , 12 ]. For example, in IL-1β-treated chondrocytes, inflammatory cytokines are obviously reduced in the METTL3 overexpression group, while IL-1β administration reverses the reduced cytokines by METTL3 overexpression [ 13 ]. In IL-1β-induced ATDC5 cells, METTL3 mRNA, as well as the m 6 A methylated mRNA of total mRNA, are increased.…”

Section: Introductionmentioning

confidence: 99%

N6-methyladenosine (m6A) methyltransferase METTL3-mediated LINC00680 accelerates osteoarthritis through m6A/SIRT1 manner

Ren

Wuermanbieke

et al. 2022

Cell Death Discov.

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Increasing evidence suggest the biological roles of N6-methyladenosine (m6A) and long noncoding RNAs (lncRNAs) in the bone disease, especially osteoarthritis (OA). However, the interaction of m6A and lncRNA in osteoarthritis is still unclear. Here, we found that a m6A-related lncRNA LINC00680 upregulated in the OA tissue and IL-1β-induced isolated primary chondrocytes. Functionally, in IL-1β-induced chondrocytes, silencing of LINC00680 recovered the proliferation and repressed the extracellular matrix (ECM) degradation. Mechanistically, m6A methyltransferase METTL3 combined tithe the m6A site of LINC00680 to up-regulate its expression. Moreover, LINC00680 interacted with SIRT1 mRNA through binding at m6A site on SIRT1 mRNA 3′-UTR, thereby enhancing the stability of SIRT1 mRNA. Overall, these findings exhibited a role of LINC00680/m6A/SIRT1 mRNA complex in chondrocytes. Taken together, the present study intends to uncover the mechanism by which METTL3-mediated LINC00680 accelerates OA progression, which may provide novel insight for OA.

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“…The detection of synovial tissue in patients with OA revealed that METTL3 could also induce autophagy by inhibiting ATG7 ( Chen X. et al, 2021 ). In addition, METTL3 may participate in OA by regulating the inflammatory response ( Sang et al, 2021 ). In summary, methylation is also an essential mechanism for pathological changes in OA.…”

Section: Pathological Change Mechanism Of Osteoarthritismentioning

confidence: 99%

Exercise for Osteoarthritis: A Literature Review of Pathology and Mechanism

Kong

Wang

Zhang

2022

Front. Aging Neurosci.

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Osteoarthritis (OA) has a very high incidence worldwide and has become a very common joint disease in the elderly. Currently, the treatment methods for OA include surgery, drug therapy, and exercise therapy. In recent years, the treatment of certain diseases by exercise has received increasing research and attention. Proper exercise can improve the physiological function of various organs of the body. At present, the treatment of OA is usually symptomatic. Limited methods are available for the treatment of OA according to its pathogenesis, and effective intervention has not been developed to slow down the progress of OA from the molecular level. Only by clarifying the mechanism of exercise treatment of OA and the influence of different exercise intensities on OA patients can we choose the appropriate exercise prescription to prevent and treat OA. This review mainly expounds the mechanism that exercise alleviates the pathological changes of OA by affecting the degradation of the ECM, apoptosis, inflammatory response, autophagy, and changes of ncRNA, and summarizes the effects of different exercise types on OA patients. Finally, it is found that different exercise types, exercise intensity, exercise time and exercise frequency have different effects on OA patients. At the same time, suitable exercise prescriptions are recommended for OA patients.

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METTL3 involves the progression of osteoarthritis probably by affecting ECM degradation and regulating the inflammatory response

Cited by 45 publications

References 30 publications

METTL3-Mediated N6-Methyladenosine Modification of Trim59 mRNA Protects Against Sepsis-Induced Acute Respiratory Distress Syndrome

METTL3-Mediated N6-Methyladenosine Modification of Trim59 mRNA Protects Against Sepsis-Induced Acute Respiratory Distress Syndrome

N6-methyladenosine (m6A) methyltransferase METTL3-mediated LINC00680 accelerates osteoarthritis through m6A/SIRT1 manner

Exercise for Osteoarthritis: A Literature Review of Pathology and Mechanism

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