title: GCN5 modulates osteogenic differentiation of periodontal ligament stem cells through DKK1 acetylation in inflammatory microenvironment.
abstract: Periodontal ligament stem cells (PDLSCs) from periodontitis patients showed defective osteogenic differentiation. However, the mechanism of impaired osteogenic differentiation of PDLSCs in inflammatory microenvironments is still unclear. In this study, we found that inflammation in the microenvironment resulted in downregulation of histone acetyltransferase GCN5 expression and lack of GCN5 caused decreased osteogenic differentiation of PDLSCs. Previous study showed activated Wnt/β-cateinin pathway of PDLSCs resulted in defective osteogenic differentiation. Here we found knockdown of GCN5 decreased the expression of DKK1, an inhibitor of Wnt/β-cateinin pathway, thus activated Wnt/β-catenin pathway of PDLSCs. Mechanistically, GCN5 regulated DKK1 expression by acetylation of Histone H3 lysine 9 (H3K9) and Histone H3 lysine 14 (H3K14) at its promoter region. Interestingly, we found that in vivo injection of aspirin rescued the periodontitis of rats through inhibiting inflammation and upregulating GCN5 expression. Furthermore, aspirin treatment of PDLSCs upregulated GCN5 expression and increased osteogenic differentiation of PDLSCs. In conclusion, GCN5 plays a protective role in periodontitis through acetylation of DKK1 and applying drugs targeting GCN5, such as aspirin, could be a new approach for periodontitis treatment.
authors.affiliation: State Key Laboratory of Military Stomatology, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.|Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Li
authors.affiliation: State Key Laboratory of Military Stomatology, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.|Department of Stomatology, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510140, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Oral and Maxillofacial surgery, General Hospital of Shenyang Military Area Command, Shenyang, Liaoning 110840, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Military Stomatology, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.|Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Xue
authors.affiliation: State Key Laboratory of Military Stomatology, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.|Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Xiaoning
authors.initials: X
authors.lastname: He
authors.affiliation: State Key Laboratory of Military Stomatology, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.|Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liao
authors.affiliation: Department of Stomatology, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510140, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Yuan
authors.affiliation: State Key Laboratory of Military Stomatology, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.|Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jin
mesh_terms: D000107:Acetylation; D000293:Adolescent; D000328:Adult; D002454:Cell Differentiation; D002478:Cells, Cultured; D015536:Down-Regulation; D005260:Female; D006657:Histones / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D010012:Osteogenesis; D010513:Periodontal Ligament / Q000166:cytology* / Q000378:metabolism; D010518:Periodontitis / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D060449:Wnt Signaling Pathway; D055815:Young Adult; D050880:p300-CBP Transcription Factors / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
chemical_list: D006657:Histones; D036341:Intercellular Signaling Peptides and Proteins; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C501126:DKK1 protein, human