Advanced glycation end products impair bone marrow mesenchymal stem cells osteogenesis in periodontitis with diabetes via FTO-mediated N 6-methyladenosine modification of sclerostin
Abstract Background Diabetes mellitus (DM) and periodontitis are two prevalent diseases with mutual influence. Accumulation of advanced glycation end products (AGEs) in hyperglycemia may impair cell function and worsen periodontal conditions. N 6-methyladenosine (m6A) is an important post-transcript...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-11-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-023-04630-5 |
| _version_ | 1797636723527647232 |
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| author | Jie Zhou Yanlin Zhu Dongqing Ai Mengjiao Zhou Han Li Guangyue Li Leilei Zheng Jinlin Song |
| author_facet | Jie Zhou Yanlin Zhu Dongqing Ai Mengjiao Zhou Han Li Guangyue Li Leilei Zheng Jinlin Song |
| author_sort | Jie Zhou |
| collection | DOAJ |
| description | Abstract Background Diabetes mellitus (DM) and periodontitis are two prevalent diseases with mutual influence. Accumulation of advanced glycation end products (AGEs) in hyperglycemia may impair cell function and worsen periodontal conditions. N 6-methyladenosine (m6A) is an important post-transcriptional modification in RNAs that regulates cell fate determinant and progression of diseases. However, whether m6A methylation participates in the process of periodontitis with diabetes is unclear. Thus, we aimed to investigate the effects of AGEs on bone marrow mesenchymal stem cells (BMSCs), elucidate the m6A modification mechanism in diabetes-associated periodontitis. Methods Periodontitis with diabetes were established by high-fat diet/streptozotocin injection and silk ligation. M6A modifications in alveolar bone were demonstrated by RNA immunoprecipitation sequence. BMSCs treated with AGEs, fat mass and obesity associated (FTO) protein knockdown and sclerostin (SOST) interference were evaluated by quantitative polymerase chain reaction, western blot, immunofluorescence, alkaline phosphatase and Alizarin red S staining. Results Diabetes damaged alveolar bone regeneration was validated in vivo. In vitro experiments showed AGEs inhibited BMSCs osteogenesis and influenced the FTO expression and m6A level in total RNA. FTO knockdown increased the m6A levels and reversed the AGE-induced inhibition of BMSCs differentiation. Mechanically, FTO regulated m6A modification on SOST transcripts, and AGEs affected the binding of FTO to SOST transcripts. FTO knockdown accelerated the degradation of SOST mRNA in presence of AGEs. Interference with SOST expression in AGE-treated BMSCs partially rescued the osteogenesis by activating Wnt Signaling. Conclusions AGEs impaired BMSCs osteogenesis by regulating SOST in an m6A-dependent manner, presenting a promising method for bone regeneration treatment of periodontitis with diabetes. |
| first_indexed | 2024-03-11T12:39:13Z |
| format | Article |
| id | doaj.art-f7bf2418e9a14fdcb324a352055f7f4c |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-03-11T12:39:13Z |
| publishDate | 2023-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-f7bf2418e9a14fdcb324a352055f7f4c2023-11-05T12:28:19ZengBMCJournal of Translational Medicine1479-58762023-11-0121111810.1186/s12967-023-04630-5Advanced glycation end products impair bone marrow mesenchymal stem cells osteogenesis in periodontitis with diabetes via FTO-mediated N 6-methyladenosine modification of sclerostinJie Zhou0Yanlin Zhu1Dongqing Ai2Mengjiao Zhou3Han Li4Guangyue Li5Leilei Zheng6Jinlin Song7College of Stomatology, Chongqing Medical UniversityCollege of Stomatology, Chongqing Medical UniversityCollege of Stomatology, Chongqing Medical UniversityCollege of Stomatology, Chongqing Medical UniversityCollege of Stomatology, Chongqing Medical UniversityCollege of Stomatology, Chongqing Medical UniversityCollege of Stomatology, Chongqing Medical UniversityCollege of Stomatology, Chongqing Medical UniversityAbstract Background Diabetes mellitus (DM) and periodontitis are two prevalent diseases with mutual influence. Accumulation of advanced glycation end products (AGEs) in hyperglycemia may impair cell function and worsen periodontal conditions. N 6-methyladenosine (m6A) is an important post-transcriptional modification in RNAs that regulates cell fate determinant and progression of diseases. However, whether m6A methylation participates in the process of periodontitis with diabetes is unclear. Thus, we aimed to investigate the effects of AGEs on bone marrow mesenchymal stem cells (BMSCs), elucidate the m6A modification mechanism in diabetes-associated periodontitis. Methods Periodontitis with diabetes were established by high-fat diet/streptozotocin injection and silk ligation. M6A modifications in alveolar bone were demonstrated by RNA immunoprecipitation sequence. BMSCs treated with AGEs, fat mass and obesity associated (FTO) protein knockdown and sclerostin (SOST) interference were evaluated by quantitative polymerase chain reaction, western blot, immunofluorescence, alkaline phosphatase and Alizarin red S staining. Results Diabetes damaged alveolar bone regeneration was validated in vivo. In vitro experiments showed AGEs inhibited BMSCs osteogenesis and influenced the FTO expression and m6A level in total RNA. FTO knockdown increased the m6A levels and reversed the AGE-induced inhibition of BMSCs differentiation. Mechanically, FTO regulated m6A modification on SOST transcripts, and AGEs affected the binding of FTO to SOST transcripts. FTO knockdown accelerated the degradation of SOST mRNA in presence of AGEs. Interference with SOST expression in AGE-treated BMSCs partially rescued the osteogenesis by activating Wnt Signaling. Conclusions AGEs impaired BMSCs osteogenesis by regulating SOST in an m6A-dependent manner, presenting a promising method for bone regeneration treatment of periodontitis with diabetes.https://doi.org/10.1186/s12967-023-04630-5Diabetes mellitusPeriodontitisBone marrow mesenchymal stem cellsOsteogenesisAdvanced glycation end productsN 6-methyladenosine |
| spellingShingle | Jie Zhou Yanlin Zhu Dongqing Ai Mengjiao Zhou Han Li Guangyue Li Leilei Zheng Jinlin Song Advanced glycation end products impair bone marrow mesenchymal stem cells osteogenesis in periodontitis with diabetes via FTO-mediated N 6-methyladenosine modification of sclerostin Journal of Translational Medicine Diabetes mellitus Periodontitis Bone marrow mesenchymal stem cells Osteogenesis Advanced glycation end products N 6-methyladenosine |
| title | Advanced glycation end products impair bone marrow mesenchymal stem cells osteogenesis in periodontitis with diabetes via FTO-mediated N 6-methyladenosine modification of sclerostin |
| title_full | Advanced glycation end products impair bone marrow mesenchymal stem cells osteogenesis in periodontitis with diabetes via FTO-mediated N 6-methyladenosine modification of sclerostin |
| title_fullStr | Advanced glycation end products impair bone marrow mesenchymal stem cells osteogenesis in periodontitis with diabetes via FTO-mediated N 6-methyladenosine modification of sclerostin |
| title_full_unstemmed | Advanced glycation end products impair bone marrow mesenchymal stem cells osteogenesis in periodontitis with diabetes via FTO-mediated N 6-methyladenosine modification of sclerostin |
| title_short | Advanced glycation end products impair bone marrow mesenchymal stem cells osteogenesis in periodontitis with diabetes via FTO-mediated N 6-methyladenosine modification of sclerostin |
| title_sort | advanced glycation end products impair bone marrow mesenchymal stem cells osteogenesis in periodontitis with diabetes via fto mediated n 6 methyladenosine modification of sclerostin |
| topic | Diabetes mellitus Periodontitis Bone marrow mesenchymal stem cells Osteogenesis Advanced glycation end products N 6-methyladenosine |
| url | https://doi.org/10.1186/s12967-023-04630-5 |
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