PSAT1 positively regulates the osteogenic lineage differentiation of periodontal ligament stem cells through the ATF4/PSAT1/Akt/GSK3β/β-catenin axis
Abstract Background Periodontal ligament stem cells (PDLSCs) are important seed cells for tissue engineering to realize the regeneration of alveolar bone. Understanding the gene regulatory mechanisms of osteogenic lineage differentiation in PDLSCs will facilitate PDLSC-based bone regeneration. Howev...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-02-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-022-03775-z |
| _version_ | 1811171586652241920 |
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| author | Linglu Jia Dongfang Li Ya-Nan Wang Dongjiao Zhang Xin Xu |
| author_facet | Linglu Jia Dongfang Li Ya-Nan Wang Dongjiao Zhang Xin Xu |
| author_sort | Linglu Jia |
| collection | DOAJ |
| description | Abstract Background Periodontal ligament stem cells (PDLSCs) are important seed cells for tissue engineering to realize the regeneration of alveolar bone. Understanding the gene regulatory mechanisms of osteogenic lineage differentiation in PDLSCs will facilitate PDLSC-based bone regeneration. However, these regulatory molecular signals have not been clarified. Methods To screen potential regulators of osteogenic differentiation, the gene expression profiles of undifferentiated and osteodifferentiated PDLSCs were compared by microarray and bioinformatics methods, and PSAT1 was speculated to be involved in the gene regulation network of osteogenesis in PDLSCs. Lentiviral vectors were used to overexpress or knock down PSAT1 in PDLSCs, and then the proliferation activity, migration ability, and osteogenic differentiation ability of PDLSCs in vitro were analysed. A rat mandibular defect model was built to analyse the regulatory effects of PSAT1 on PDLSC-mediated bone regeneration in vivo. The regulation of PSAT1 on the Akt/GSK3β/β-catenin signalling axis was analysed using the Akt phosphorylation inhibitor Ly294002 or agonist SC79. The potential sites on the promoter of PSAT1 that could bind to the transcription factor ATF4 were predicted and verified. Results The microarray assay showed that the expression levels of 499 genes in PDLSCs were altered significantly after osteogenic induction. Among these genes, the transcription level of PSAT1 in osteodifferentiated PDLSCs was much lower than that in undifferentiated PDLSCs. Overexpressing PSAT1 not only enhanced the proliferation and osteogenic differentiation abilities of PDLSCs in vitro, but also promoted PDLSC-based alveolar bone regeneration in vivo, while knocking down PSAT1 had the opposite effects in PDLSCs. Mechanistic experiments suggested that PSAT1 regulated the osteogenic lineage fate of PDLSCs through the Akt/GSK3β/β-catenin signalling axis. PSAT1 expression in PDLSCs during osteogenic differentiation was controlled by transcription factor ATF4, which is realized by the combination of ATF4 and the PSAT1 promoter. Conclusion PSAT1 is a potential important regulator of the osteogenic lineage differentiation of PDLSCs through the ATF4/PSAT1/Akt/GSK3β/β-catenin signalling pathway. PSAT1 could be a candidate gene modification target for enhancing PDLSCs-based bone regeneration. |
| first_indexed | 2024-04-10T17:16:32Z |
| format | Article |
| id | doaj.art-bd31252974c846dfb44eed14adb7a90e |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-10T17:16:32Z |
| publishDate | 2023-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-bd31252974c846dfb44eed14adb7a90e2023-02-05T12:22:20ZengBMCJournal of Translational Medicine1479-58762023-02-0121111910.1186/s12967-022-03775-zPSAT1 positively regulates the osteogenic lineage differentiation of periodontal ligament stem cells through the ATF4/PSAT1/Akt/GSK3β/β-catenin axisLinglu Jia0Dongfang Li1Ya-Nan Wang2Dongjiao Zhang3Xin Xu4Department of Prosthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong UniversityShandong Key Laboratory of Oral Tissue RegenerationDepartment of Implantology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong UniversityDepartment of Implantology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong UniversityDepartment of Implantology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong UniversityAbstract Background Periodontal ligament stem cells (PDLSCs) are important seed cells for tissue engineering to realize the regeneration of alveolar bone. Understanding the gene regulatory mechanisms of osteogenic lineage differentiation in PDLSCs will facilitate PDLSC-based bone regeneration. However, these regulatory molecular signals have not been clarified. Methods To screen potential regulators of osteogenic differentiation, the gene expression profiles of undifferentiated and osteodifferentiated PDLSCs were compared by microarray and bioinformatics methods, and PSAT1 was speculated to be involved in the gene regulation network of osteogenesis in PDLSCs. Lentiviral vectors were used to overexpress or knock down PSAT1 in PDLSCs, and then the proliferation activity, migration ability, and osteogenic differentiation ability of PDLSCs in vitro were analysed. A rat mandibular defect model was built to analyse the regulatory effects of PSAT1 on PDLSC-mediated bone regeneration in vivo. The regulation of PSAT1 on the Akt/GSK3β/β-catenin signalling axis was analysed using the Akt phosphorylation inhibitor Ly294002 or agonist SC79. The potential sites on the promoter of PSAT1 that could bind to the transcription factor ATF4 were predicted and verified. Results The microarray assay showed that the expression levels of 499 genes in PDLSCs were altered significantly after osteogenic induction. Among these genes, the transcription level of PSAT1 in osteodifferentiated PDLSCs was much lower than that in undifferentiated PDLSCs. Overexpressing PSAT1 not only enhanced the proliferation and osteogenic differentiation abilities of PDLSCs in vitro, but also promoted PDLSC-based alveolar bone regeneration in vivo, while knocking down PSAT1 had the opposite effects in PDLSCs. Mechanistic experiments suggested that PSAT1 regulated the osteogenic lineage fate of PDLSCs through the Akt/GSK3β/β-catenin signalling axis. PSAT1 expression in PDLSCs during osteogenic differentiation was controlled by transcription factor ATF4, which is realized by the combination of ATF4 and the PSAT1 promoter. Conclusion PSAT1 is a potential important regulator of the osteogenic lineage differentiation of PDLSCs through the ATF4/PSAT1/Akt/GSK3β/β-catenin signalling pathway. PSAT1 could be a candidate gene modification target for enhancing PDLSCs-based bone regeneration.https://doi.org/10.1186/s12967-022-03775-zPSAT1Periodontal ligament stem cellsOsteogenic differentiationMicroarray assay |
| spellingShingle | Linglu Jia Dongfang Li Ya-Nan Wang Dongjiao Zhang Xin Xu PSAT1 positively regulates the osteogenic lineage differentiation of periodontal ligament stem cells through the ATF4/PSAT1/Akt/GSK3β/β-catenin axis Journal of Translational Medicine PSAT1 Periodontal ligament stem cells Osteogenic differentiation Microarray assay |
| title | PSAT1 positively regulates the osteogenic lineage differentiation of periodontal ligament stem cells through the ATF4/PSAT1/Akt/GSK3β/β-catenin axis |
| title_full | PSAT1 positively regulates the osteogenic lineage differentiation of periodontal ligament stem cells through the ATF4/PSAT1/Akt/GSK3β/β-catenin axis |
| title_fullStr | PSAT1 positively regulates the osteogenic lineage differentiation of periodontal ligament stem cells through the ATF4/PSAT1/Akt/GSK3β/β-catenin axis |
| title_full_unstemmed | PSAT1 positively regulates the osteogenic lineage differentiation of periodontal ligament stem cells through the ATF4/PSAT1/Akt/GSK3β/β-catenin axis |
| title_short | PSAT1 positively regulates the osteogenic lineage differentiation of periodontal ligament stem cells through the ATF4/PSAT1/Akt/GSK3β/β-catenin axis |
| title_sort | psat1 positively regulates the osteogenic lineage differentiation of periodontal ligament stem cells through the atf4 psat1 akt gsk3β β catenin axis |
| topic | PSAT1 Periodontal ligament stem cells Osteogenic differentiation Microarray assay |
| url | https://doi.org/10.1186/s12967-022-03775-z |
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