Background: Congenital pseudarthrosis of the tibia (CPT) is a dominant health challenge in pediatric orthopedics. The essential process in the development of CPT is the limited capacity of mesenchymal stem cells (MSCs) derived from CPT to undergo osteogenic differentiation. Our research aimed to elucidate the role and mechanism of methyltransferase-like 3 (METTL3) in the osteogenic differentiation process of CPT MSCs.
Methods: The osteogenic differentiation medium was used to culture MSCs, and the detection of osteogenic differentiation was performed using Alizarin Red S and alkaline phosphatase (ALP) assays. Gene or protein expression was assessed by quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, or immunofluorescence (IF) staining. The mA modification of Homeobox D8 (HOXD8) was verified by methylated RNA immunoprecipitation (MeRIP) assay. Interactions between METTL3 and HOXD8 or HOXD8 and integrin alpha 5 (ITGA5) promoter were validated by the luciferase reporter gene, RIP, and chromatin immunoprecipitation (ChIP) assays.
Results: METTL3 overexpression enhanced CPT MSCs' osteogenic differentiation. METTL3 stabilized the HOXD8 in an mA-dependent manner. Moreover, the overexpressed ITGA5 up-regulated the CPT MSCs' osteogenic differentiation. Further, HOXD8 could transcriptionally activate ITGA5. METTL3 increased the transcription of ITGA5 via HOXD8 to enhance the osteogenic differentiation of CPT MSCs.
Conclusion: METTL3 promoted osteogenic differentiation via modulating the HOXD8/ITGA5 axis in CPT MSCs.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11137358 | PMC |
| http://dx.doi.org/10.1016/j.reth.2024.04.004 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
380 MPa-30% grade biodegradable Zn-Mn-Mg-Ca alloy: Bimodal grain structure, large work-hardening strain, and enhanced biocompatibility.
Acta Biomater
December 2024
Beijing Advanced Innovation Center for Materials Genome Engineering, State Key Laboratory for Advanced Metals and Materials, School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing 100083, PR China; Institute of Materials Intelligent Technology, Liaoning Academy of Materials, Shenyang 110004, China. Electronic address:
Strain softening is a common issue for high-strength biodegradable Zn alloys. We developed Zn-0.6Mn-0.
View Article and Find Full Text PDFNitrided Ti-6Al-4V: A Catalyst for Increase Mineralization and Osteogenic Marker Expression.
J Biomed Mater Res A
January 2025
Biomedical Engineering Institute, Chiang Mai University, Chiang Mai, Thailand.
Plasma nitriding is one of the surface modifications that show more effectiveness than other methods. In this study, the plasma-based ion implantation (PBII) technique was performed on the surface of titanium alloy (Ti-6Al-4V, Ti64) using a mixture of nitrogen (N) and argon (Ar), resulting in a plasma-nitrided surface (TiN-Ti64). The surface composition of the TiN-Ti64 was verified through X-ray photoelectron spectroscopy (XPS).
View Article and Find Full Text PDFMETTL3-mediated m6A modifications of NLRP3 accelerate alveolar bone resorption through enhancing macrophage pyroptosis.
Cell Signal
December 2024
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China; Department of Periodontology, School & Hospital of Stomatology, Wuhan University, Wuhan, China. Electronic address:
Periodontitis (PD) is twice as prevalent in diabetics compared to nondiabetics, and diabetes-associated PD is characterized by increased inflammation and aggravated tissue damage. Pyroptosis has recently been implicated in diabetes-associated PD; however, the underlying mechanisms remain largely unknown, resulting in a lack of effective treatments. In this study, we investigated the role of methyltransferase-like 3 (METTL3) in macrophage pyroptosis and found that it inhibits the osteogenic differentiation of osteoblasts via pyroptotic macrophages in a diabetes-associated periodontitis mouse model.
View Article and Find Full Text PDFLiraglutide promotes osteogenic differentiation of mesenchymal stem cells by inhibiting M1 macrophage polarization and CXCL9 release in vitro.
Mol Cell Endocrinol
December 2024
Implant Department, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Tiantan Xili No.4, Dongcheng District, Beijing, 100050, China. Electronic address:
As a GLP-1 receptor agonist widely used in treating type 2 diabetes, liraglutide shows potential applications in bone tissue engineering. This study investigated liraglutide's direct effects on rat bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation and its regulatory mechanism through macrophage polarization. Results showed that liraglutide significantly enhanced BMSC migration and osteogenic differentiation.
View Article and Find Full Text PDFMethacrylated silk fibroin based composite hydrogel with ROS-scavenging and osteogenic ability to orchestrate diabetic bone regeneration.
Int J Biol Macromol
December 2024
Department of Orthopedics, Peking University Third Hospital, Beijing, China; Engineering Research Center of Bone and Joint Precision Medicine, Beijing, China. Electronic address:
The repair of diabetic bone defects is still filled with enormous challenges. Excessive reactive oxygen species (ROS) are regenerated in diabetic bone defect sites which is harmful to bone regeneration. Therefore, it's to a good strategy to scavenge the excess ROS to provide a friendly environment for diabetic bone defects repair.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!