Transcriptome analysis reveals the mechanism of stromal cell-derived factor-1 and exendin-4 synergistically promoted periodontal ligament stem cells osteogenic differentiation

Stromal cell-derived factor-1 (SDF-1) and Exendin-4 (EX-4) play beneficial roles in promoting periodontal ligament stem cells (PDLSCs) osteogenic differentiation, while the detailed mechanism has not been clarified. In this study, we aimed to evaluate the biological mechanism of SDF-1 and EX-4 alone...

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Main Authors: Wenyan Kang, Lingqian Du, Qianyu Liang, Rui Zhang, Chunxu Lv, Shaohua Ge
Format: Article
Language:English
Published: PeerJ Inc. 2021-08-01
Series:PeerJ
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Online Access:https://peerj.com/articles/12091.pdf
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author Wenyan Kang
Lingqian Du
Qianyu Liang
Rui Zhang
Chunxu Lv
Shaohua Ge
author_facet Wenyan Kang
Lingqian Du
Qianyu Liang
Rui Zhang
Chunxu Lv
Shaohua Ge
author_sort Wenyan Kang
collection DOAJ
description Stromal cell-derived factor-1 (SDF-1) and Exendin-4 (EX-4) play beneficial roles in promoting periodontal ligament stem cells (PDLSCs) osteogenic differentiation, while the detailed mechanism has not been clarified. In this study, we aimed to evaluate the biological mechanism of SDF-1 and EX-4 alone or synergistic application in regulating PDLSCs differentiation by RNA-sequencing (RNA-seq). A total of 110, 116 and 109 differentially expressed genes (DEGs) were generated in osteogenic medium induced PDLSCs treated by SDF-1, EX-4, and SDF-1+EX-4, respectively. The DEGs in SDF-1 group were enriched in signal transduction related signaling pathways; the DEGs in EX-4 group were enriched in metabolism and biosynthesis-related pathways; and the DEGs generated in SDF-1+EX-4 group were mainly enriched in RNA polymerase II transcription, cell differentiation, chromatin organization, protein phosphorylation pathways. Based on Venn analysis, a total of 37 specific DEGs were identified in SDF-1+EX-4 group, which were mainly enriched in negative regulation of autophagy and cellular component disassembly signaling pathways. Short time-series expression miner (STEM) analysis grouped all expressed genes of PDLSCs into 49 clusters according to the dynamic expression patterns and 25 genes, including NRSN2, CHD9, TUBA1A, distributed in 10 gene clusters in SDF-1+EX-4 treated PDLSCs were significantly up-regulated compared with the SDF-1 and EX-4 alone groups. The gene set enrichment analysis indicated that SDF-1 could amplify the role of EX-4 in regulating varied signaling pathways, such as type II diabetes mellitus and insulin signaling pathways; while EX-4 could aggravate the effect of SDF-1 on PDLSCs biological roles via regulating primary immunodeficiency, tight junction signaling pathways. In summary, our study confirmed that SDF-1 and EX-4 combined application could enhance PDLSCs biological activity and promote PDLSCs osteogenic differentiation by regulating the metabolism, biosynthesis and immune-related signaling pathways.
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spelling doaj.art-1f84e7a89f6546899ea5ae5d89425f482023-12-03T11:02:39ZengPeerJ Inc.PeerJ2167-83592021-08-019e1209110.7717/peerj.12091Transcriptome analysis reveals the mechanism of stromal cell-derived factor-1 and exendin-4 synergistically promoted periodontal ligament stem cells osteogenic differentiationWenyan Kang0Lingqian Du1Qianyu Liang2Rui Zhang3Chunxu Lv4Shaohua Ge5Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shandong, ChinaDepartment of Stomatology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, ChinaDepartment of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shandong, ChinaDepartment of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shandong, ChinaDepartment of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shandong, ChinaDepartment of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shandong, ChinaStromal cell-derived factor-1 (SDF-1) and Exendin-4 (EX-4) play beneficial roles in promoting periodontal ligament stem cells (PDLSCs) osteogenic differentiation, while the detailed mechanism has not been clarified. In this study, we aimed to evaluate the biological mechanism of SDF-1 and EX-4 alone or synergistic application in regulating PDLSCs differentiation by RNA-sequencing (RNA-seq). A total of 110, 116 and 109 differentially expressed genes (DEGs) were generated in osteogenic medium induced PDLSCs treated by SDF-1, EX-4, and SDF-1+EX-4, respectively. The DEGs in SDF-1 group were enriched in signal transduction related signaling pathways; the DEGs in EX-4 group were enriched in metabolism and biosynthesis-related pathways; and the DEGs generated in SDF-1+EX-4 group were mainly enriched in RNA polymerase II transcription, cell differentiation, chromatin organization, protein phosphorylation pathways. Based on Venn analysis, a total of 37 specific DEGs were identified in SDF-1+EX-4 group, which were mainly enriched in negative regulation of autophagy and cellular component disassembly signaling pathways. Short time-series expression miner (STEM) analysis grouped all expressed genes of PDLSCs into 49 clusters according to the dynamic expression patterns and 25 genes, including NRSN2, CHD9, TUBA1A, distributed in 10 gene clusters in SDF-1+EX-4 treated PDLSCs were significantly up-regulated compared with the SDF-1 and EX-4 alone groups. The gene set enrichment analysis indicated that SDF-1 could amplify the role of EX-4 in regulating varied signaling pathways, such as type II diabetes mellitus and insulin signaling pathways; while EX-4 could aggravate the effect of SDF-1 on PDLSCs biological roles via regulating primary immunodeficiency, tight junction signaling pathways. In summary, our study confirmed that SDF-1 and EX-4 combined application could enhance PDLSCs biological activity and promote PDLSCs osteogenic differentiation by regulating the metabolism, biosynthesis and immune-related signaling pathways.https://peerj.com/articles/12091.pdfPeriodontal ligament stem cellsStromal cell-derived factor-1Exendin-4Osteogenic differentiationRNA-seq
spellingShingle Wenyan Kang
Lingqian Du
Qianyu Liang
Rui Zhang
Chunxu Lv
Shaohua Ge
Transcriptome analysis reveals the mechanism of stromal cell-derived factor-1 and exendin-4 synergistically promoted periodontal ligament stem cells osteogenic differentiation
PeerJ
Periodontal ligament stem cells
Stromal cell-derived factor-1
Exendin-4
Osteogenic differentiation
RNA-seq
title Transcriptome analysis reveals the mechanism of stromal cell-derived factor-1 and exendin-4 synergistically promoted periodontal ligament stem cells osteogenic differentiation
title_full Transcriptome analysis reveals the mechanism of stromal cell-derived factor-1 and exendin-4 synergistically promoted periodontal ligament stem cells osteogenic differentiation
title_fullStr Transcriptome analysis reveals the mechanism of stromal cell-derived factor-1 and exendin-4 synergistically promoted periodontal ligament stem cells osteogenic differentiation
title_full_unstemmed Transcriptome analysis reveals the mechanism of stromal cell-derived factor-1 and exendin-4 synergistically promoted periodontal ligament stem cells osteogenic differentiation
title_short Transcriptome analysis reveals the mechanism of stromal cell-derived factor-1 and exendin-4 synergistically promoted periodontal ligament stem cells osteogenic differentiation
title_sort transcriptome analysis reveals the mechanism of stromal cell derived factor 1 and exendin 4 synergistically promoted periodontal ligament stem cells osteogenic differentiation
topic Periodontal ligament stem cells
Stromal cell-derived factor-1
Exendin-4
Osteogenic differentiation
RNA-seq
url https://peerj.com/articles/12091.pdf
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