Specific RNA m6A modification sites in bone marrow mesenchymal stem cells from the jawbone marrow of type 2 diabetes patients with dental implant failure
Abstract The failure rate of dental implantation in patients with well-controlled type 2 diabetes mellitus (T2DM) is higher than that in non-diabetic patients. This due, in part, to the impaired function of bone marrow mesenchymal stem cells (BMSCs) from the jawbone marrow of T2DM patients (DM-BMSCs...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2023-01-01
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| Series: | International Journal of Oral Science |
| Online Access: | https://doi.org/10.1038/s41368-022-00202-3 |
| _version_ | 1797952646529679360 |
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| author | Wanhao Yan Xiao Lin Yiqian Ying Jun Li Zhipeng Fan |
| author_facet | Wanhao Yan Xiao Lin Yiqian Ying Jun Li Zhipeng Fan |
| author_sort | Wanhao Yan |
| collection | DOAJ |
| description | Abstract The failure rate of dental implantation in patients with well-controlled type 2 diabetes mellitus (T2DM) is higher than that in non-diabetic patients. This due, in part, to the impaired function of bone marrow mesenchymal stem cells (BMSCs) from the jawbone marrow of T2DM patients (DM-BMSCs), limiting implant osseointegration. RNA N6-methyladenine (m6A) is important for BMSC function and diabetes regulation. However, it remains unclear how to best regulate m6A modifications in DM-BMSCs to enhance function. Based on the “m6A site methylation stoichiometry” of m6A single nucleotide arrays, we identified 834 differential m6A-methylated genes in DM-BMSCs compared with normal-BMSCs (N-BMSCs), including 43 and 790 m6A hypermethylated and hypomethylated genes, respectively, and 1 gene containing hyper- and hypomethylated m6A sites. Differential m6A hypermethylated sites were primarily distributed in the coding sequence, while hypomethylated sites were mainly in the 3′-untranslated region. The largest and smallest proportions of m6A-methylated genes were on chromosome 1 and 21, respectively. MazF-PCR and real-time RT-PCR results for the validation of erythrocyte membrane protein band 4.1 like 3, activity-dependent neuroprotector homeobox (ADNP), growth differentiation factor 11 (GDF11), and regulator of G protein signalling 2 agree with m6A single nucleotide array results; ADNP and GDF11 mRNA expression decreased in DM-BMSCs. Furthermore, gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses suggested that most of these genes were enriched in metabolic processes. This study reveals the differential m6A sites of DM-BMSCs compared with N-BMSCs and identifies candidate target genes to enhance BMSC function and improve implantation success in T2DM patients. |
| first_indexed | 2024-04-10T22:50:45Z |
| format | Article |
| id | doaj.art-b78464c559b64f9fb4b528b382604777 |
| institution | Directory Open Access Journal |
| issn | 2049-3169 |
| language | English |
| last_indexed | 2024-04-10T22:50:45Z |
| publishDate | 2023-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | International Journal of Oral Science |
| spelling | doaj.art-b78464c559b64f9fb4b528b3826047772023-01-15T12:05:52ZengNature Publishing GroupInternational Journal of Oral Science2049-31692023-01-0115111310.1038/s41368-022-00202-3Specific RNA m6A modification sites in bone marrow mesenchymal stem cells from the jawbone marrow of type 2 diabetes patients with dental implant failureWanhao Yan0Xiao Lin1Yiqian Ying2Jun Li3Zhipeng Fan4Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of StomatologyDepartment of Dental Implant Center, Beijing Stomatological Hospital, School of Stomatology, Capital Medical UniversityDepartment of Oral Implantology, Tianjin Stomatological Hospital, School of Medicine, Nankai UniversityDepartment of Dental Implant Center, Beijing Stomatological Hospital, School of Stomatology, Capital Medical UniversityLaboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of StomatologyAbstract The failure rate of dental implantation in patients with well-controlled type 2 diabetes mellitus (T2DM) is higher than that in non-diabetic patients. This due, in part, to the impaired function of bone marrow mesenchymal stem cells (BMSCs) from the jawbone marrow of T2DM patients (DM-BMSCs), limiting implant osseointegration. RNA N6-methyladenine (m6A) is important for BMSC function and diabetes regulation. However, it remains unclear how to best regulate m6A modifications in DM-BMSCs to enhance function. Based on the “m6A site methylation stoichiometry” of m6A single nucleotide arrays, we identified 834 differential m6A-methylated genes in DM-BMSCs compared with normal-BMSCs (N-BMSCs), including 43 and 790 m6A hypermethylated and hypomethylated genes, respectively, and 1 gene containing hyper- and hypomethylated m6A sites. Differential m6A hypermethylated sites were primarily distributed in the coding sequence, while hypomethylated sites were mainly in the 3′-untranslated region. The largest and smallest proportions of m6A-methylated genes were on chromosome 1 and 21, respectively. MazF-PCR and real-time RT-PCR results for the validation of erythrocyte membrane protein band 4.1 like 3, activity-dependent neuroprotector homeobox (ADNP), growth differentiation factor 11 (GDF11), and regulator of G protein signalling 2 agree with m6A single nucleotide array results; ADNP and GDF11 mRNA expression decreased in DM-BMSCs. Furthermore, gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses suggested that most of these genes were enriched in metabolic processes. This study reveals the differential m6A sites of DM-BMSCs compared with N-BMSCs and identifies candidate target genes to enhance BMSC function and improve implantation success in T2DM patients.https://doi.org/10.1038/s41368-022-00202-3 |
| spellingShingle | Wanhao Yan Xiao Lin Yiqian Ying Jun Li Zhipeng Fan Specific RNA m6A modification sites in bone marrow mesenchymal stem cells from the jawbone marrow of type 2 diabetes patients with dental implant failure International Journal of Oral Science |
| title | Specific RNA m6A modification sites in bone marrow mesenchymal stem cells from the jawbone marrow of type 2 diabetes patients with dental implant failure |
| title_full | Specific RNA m6A modification sites in bone marrow mesenchymal stem cells from the jawbone marrow of type 2 diabetes patients with dental implant failure |
| title_fullStr | Specific RNA m6A modification sites in bone marrow mesenchymal stem cells from the jawbone marrow of type 2 diabetes patients with dental implant failure |
| title_full_unstemmed | Specific RNA m6A modification sites in bone marrow mesenchymal stem cells from the jawbone marrow of type 2 diabetes patients with dental implant failure |
| title_short | Specific RNA m6A modification sites in bone marrow mesenchymal stem cells from the jawbone marrow of type 2 diabetes patients with dental implant failure |
| title_sort | specific rna m6a modification sites in bone marrow mesenchymal stem cells from the jawbone marrow of type 2 diabetes patients with dental implant failure |
| url | https://doi.org/10.1038/s41368-022-00202-3 |
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