FTO-mediated SMAD2 m6A modification protects cartilage against Osteoarthritis DOI Creative Commons
Hongyi Zhou, Ziang Xie, Yu Qian

et al.

Experimental & Molecular Medicine, Journal Year: 2024, Volume and Issue: 56(10), P. 2283 - 2295

Published: Oct. 3, 2024

Abstract N6-methyladenosine (m6A) modification is one of the most prevalent forms epigenetic and plays an important role in development degenerative diseases such as osteoarthritis (OA). However, evidence concerning m6A OA insufficient. Here, was increased human cartilage degenerated chondrocytes. Among all enzymes, expression demethylase fat mass obesity-associated protein (FTO) decreased dramatically. Conditional knockout FTO chondrocytes accelerates progression. transcription regulated by runt-related factor-1 (RUNX1). Reduced elevates at adenosine N6 position SMAD family member 2 (SMAD2) mRNA, whose stability subsequently modulated recruited reader YTH RNA binding F2 (YTHDF2). Collectively, these findings reveal function mechanism Therefore, reducing to increase SMAD2 activating might be a potential therapeutic strategy for treatment.

Language: Английский

Exercise for Osteoarthritis: A Literature Review of Pathology and Mechanism DOI Creative Commons
Hui Kong, Xue‐Qiang Wang, Xinan Zhang

et al.

Frontiers in Aging Neuroscience, Journal Year: 2022, Volume and Issue: 14

Published: May 3, 2022

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

Language: Английский

Citations

43
Engineering exosomes by three-dimensional porous scaffold culture of human umbilical cord mesenchymal stem cells promote osteochondral repair DOI Creative Commons

Zineng Yan,

Han Yin,

Jiang Wu

et al.

Materials Today Bio, Journal Year: 2023, Volume and Issue: 19, P. 100549 - 100549

Published: Jan. 20, 2023

Improving the poor microenvironment in joint cavity has potential for treating cartilage injury, and mesenchymal stem cell (MSC)-derived exosomes (MSC-Exos), which can modulate cellular behavior, are becoming a new cell-free therapy repair. Here, we used acellular extracellular matrix (ACECM) to prepare 3D scaffolds 2D substrates by low-temperature deposition modeling (LDM) tape casting. We aimed investigate whether MSC-Exos cultured on of different dimensions could improve caused injury explore related mechanisms. In vitro experiments showed that derived from MSCs three-dimensional (3D) (3D-Exos) had increased efficiency. short-term animal experiments, compared with two-dimensional (2D) environment (2D-Exos), 3D-Exos stronger ability regulate microenvironment. Long-term studies confirmed therapeutic efficacy over 2D-Exos. Thus, were applied rat knee osteochondral defect model after adsorption micropores scaffold combined subsequent articular injections, they repair ability. These findings provide strategy repairing damage. Furthermore, miRNA sequencing indicated function may be associated high expression miRNAs. our study provides valuable insights design promote regeneration.

Language: Английский

Citations

28
WTAP-mediated m6A modification of FRZB triggers the inflammatory response via the Wnt signaling pathway in osteoarthritis DOI Creative Commons

Xueying An,

Rongliang Wang,

Zhongyang Lv

et al.

Experimental & Molecular Medicine, Journal Year: 2024, Volume and Issue: 56(1), P. 156 - 167

Published: Jan. 4, 2024

Abstract Osteoarthritis (OA) is the most common form of arthritis. However, exact pathogenesis remains unclear. Emerging evidence shows that N6-methyladenosine (m 6 A) modification may have an important role in OA pathogenesis. This study aimed to investigate m A writers and underlying mechanisms osteoarthritic cartilage. Among methyltransferases, Wilms tumor 1-associated protein (WTAP) expression significantly differed clinical WTAP regulated extracellular matrix (ECM) degradation, inflammation antioxidation human chondrocytes. Mechanistically, relative downstream targets cartilage were assessed by methylated RNA immunoprecipitation sequencing (MeRIP-seq) sequencing, which indicated frizzled-related (FRZB), a secreted Wnt antagonist, was abnormally decreased accompanied high In vitro dysregulated had positive effects on β-catenin targeting FRZB, finally contributed injury phenotype Intra-articular injection adeno-associated virus-WTAP alleviated progression mouse model, while this protective effect could be reversed application Wnt/β-catenin activator. summary, revealed WTAP-dependent pathway activation through post-transcriptional regulation FRZB mRNA, thus providing potentially effective therapeutic strategy for treatment.

Language: Английский

Citations

14
Mechanistic and therapeutic insights into the function of N6-methyladenosine in arthritic diseases DOI
Xinyue Zhou,

Yajie Wu,

Yingqiu Song

et al.

Inflammation Research, Journal Year: 2025, Volume and Issue: 74(1)

Published: Jan. 7, 2025

Language: Английский

Citations

1
Overexpression of FTO alleviates osteoarthritis by regulating the processing of miR-515-5p and the TLR4/MyD88/NF-κB axis DOI

Dongfeng Cai,

Jing Zhang, Jin Yang

et al.

International Immunopharmacology, Journal Year: 2022, Volume and Issue: 114, P. 109524 - 109524

Published: Dec. 18, 2022

Language: Английский

Citations

36
Novel insights into the interaction between N6‐methyladenosine methylation and noncoding RNAs in musculoskeletal disorders DOI
Juanjuan Han, Hui Kong, Xue‐Qiang Wang

et al.

Cell Proliferation, Journal Year: 2022, Volume and Issue: 55(10)

Published: June 23, 2022

Abstract Background Musculoskeletal disorder (MSD) are a class of inflammatory and degener‐ative diseases, but the precise molecular mechanisms still poorly understood. Noncoding RNA (ncRNA) N6‐methyladenosine (m6A) modification plays an essential role in pathophysiological process MSD. This review summarized interaction between m6A methylation ncRNAs regulatory mechanism It provides new perspective for ncRNA targeted therapy Methods A comprehensive search databases was conducted with musculoskeletal disorders, noncoding RNA, N6‐methyladenosine, intervertebral disc degeneration, osteoporosis, osteosarcoma, osteoarthritis, skeletal muscle, bone, cartilage as key‐words. Then, all relevant articles. Results Intervertebral degeneration (IDD), osteoporosis (OP), osteosarcoma (OS), osteoarthritis (OA) common MSDs that affect cartilage, joint, leading to limited movement, pain, disability. However, pathogenesis remains unclear, no effective treatment drug is available at present. Numerous studies confirmed mutual regulation (i.e., microRNAs, long ncRNAs, circular RNAs) found MSD, can regulate also target regulators. by regulating homeostasis cartilage. Conclusion interacts multiple biological processes important roles IDD, OP, OS, OA. These provide insights into MSD targeting m6A‐modified may be promising approach.

Language: Английский

Citations

34
The crucial mechanism and therapeutic implication of RNA methylation in bone pathophysiology DOI
Chuan Yang, Zicai Dong,

Zhiguo Ling

et al.

Ageing Research Reviews, Journal Year: 2022, Volume and Issue: 79, P. 101641 - 101641

Published: May 13, 2022

Language: Английский

Citations

29
YTHDF2-mediated FGF14-AS2 decay promotes osteolytic metastasis of breast cancer by enhancing RUNX2 mRNA translation DOI
Ming Zhang, Jue Wang, Yucui Jin

et al.

British Journal of Cancer, Journal Year: 2022, Volume and Issue: 127(12), P. 2141 - 2153

Published: Oct. 10, 2022

Language: Английский

Citations

23
Expression pattern analysis of m6A regulators reveals IGF2BP3 as a key modulator in osteoarthritis synovial macrophages DOI Creative Commons
Yuheng Lu, Hongbo Zhang,

Haoyan Pan

et al.

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: May 22, 2023

Abstract Background Disruption of N6 methyl adenosine (m6A) modulation hampers gene expression and cellular functions, leading to various illnesses. However, the role m6A modification in osteoarthritis (OA) synovitis remains unclear. This study aimed explore patterns regulators OA synovial cell clusters identify key that mediate macrophage phenotypes. Methods The synovium were illustrated by analyzing bulk RNA-seq data. Next, we built an LASSO-Cox regression prediction model core regulators. Potential target genes these identified data from RM2target database. A molecular functional network based on their was constructed using STRING Single-cell collected verify effects clusters. Conjoint analyses single-cell performed validate correlation between regulators, clusters, disease conditions. After IGF2BP3 screened as a potential modulator macrophages, level tested its functions further overexpression knockdown vitro. Results showed aberrant Based well-fitting comprising six factors (FTO, YTHDC1, METTL5, IGF2BP3, ZC3H13, HNRNPC). indicated closely associated with phenotypic alterations. Among reader mediator. Finally, upregulation verified synovium, which promoted M1 polarization inflammation. Conclusions Our findings revealed highlighted association enhanced inflammation providing novel targets for diagnosis treatment.

Language: Английский

Citations

16
METTL3-mediated m6A modification of IGFBP7-OT promotes osteoarthritis progression by regulating the DNMT1/DNMT3a-IGFBP7 axis DOI Creative Commons
Yuting Tang,

Fangling Hong,

Siyang Ding

et al.

Cell Reports, Journal Year: 2023, Volume and Issue: 42(6), P. 112589 - 112589

Published: June 1, 2023

Osteoarthritis (OA) is the most common degenerative disorder, affecting approximately half of elderly population. In this study, we find that expressions long noncoding RNA (lncRNA) IGFBP7-OT and its maternal gene, IGFBP7, are upregulated positively correlated in osteoarthritic cartilage. Overexpression significantly inhibits chondrocyte viability, promotes apoptosis, reduces extracellular matrix components, whereas knockdown has opposite effects. overexpression cartilage degeneration markedly aggravates monosodium iodoacetate-induced OA phenotype vivo. Further mechanistic research reveals progression by upregulating IGFBP7 expression. Specifically, suppresses occupancy DNMT1 DNMT3a on promoter, thereby inhibiting methylation promoter. The upregulation partially controlled METTL3-mediated N6-methyladenosine (m6A) modification. Collectively, our findings reveal m6A modification regulating DNMT1/DNMT3a-IGFBP7 axis provide a potential therapeutical target for treatment.

Language: Английский

Citations

16