Format

Send to

Choose Destination
Stem Cells Dev. 2019 Jul 22. doi: 10.1089/scd.2019.0125. [Epub ahead of print]

Histone Methylation Mechanisms Modulate the Inflammatory Response of Periodontal Ligament Progenitors.

Author information

1
1Department of Periodontics, Center for Craniofacial Research and Diagnosis, Texas A&M College of Dentistry, Dallas, Texas.
2
2Department of Oral Biology, UIC College of Dentistry, Chicago, Illinois.
3
3Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Stomatological Hospital of Guangzhou Medical University, Guangzhou, China.
4
4Department of Stomatology, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, China.
5
5Department of Periodontics, UIC College of Dentistry, Chicago, Illinois.

Abstract

Inflammatory conditions affect periodontal ligament (PDL) homeostasis and diminish its regenerative capacity. The complexity of biological activities during an inflammatory response depends on genetic and epigenetic mechanisms. To characterize the epigenetic changes in response to periodontal pathogens we have focused on histone lysine methylation as a relatively stable chromatin modification involved in the epigenetic activation and repression of transcription and a prime candidate mechanism responsible for the exacerbated and prolonged response of periodontal cells and tissues to dental plaque biofilm. To determine the effect of inflammatory conditions on histone methylation profiles, related gene expression and cellular functions of human periodontal ligament (hPDL) progenitor cells, a hPDL cell culture system was subjected to bacterial cell wall toxin exposure [lipopolysaccharide (LPS)]. Chromatin immunoprecipitation-on-chip analysis revealed that healthy PDL cells featured high enrichment levels for the active H3K4me3 mark at COL1A1, COL3, and RUNX2 gene promoters, whereas there were high occupancy levels for the repressive H3K27me3 marks at DEFA4, CCL5, and IL-1β gene promoters. In response to LPS, H3K27me3 enrichment increased on extracellular matrix and osteogenesis lineage gene promoters, whereas H3K4me3 enrichment increased on the promoters of inflammatory response genes, suggestive of an involvement of epigenetic mechanisms in periodontal lineage differentiation and in the coordination of the periodontal inflammatory response. On a gene expression level, LPS treatment downregulated COL1A1, COL3A1, and RUNX2 expression and upregulated CCL5, DEFA4, and IL-1β gene expression. LPS also greatly affected PDL progenitor function, including a reduction in proliferation and differentiation potential and an increase in cell migration capacity. Confirming the role of epigenetic mechanisms in periodontal inflammatory conditions, our studies highlight the significant role of histone methylation mechanisms and modification enzymes in the inflammatory response to LPS bacterial cell wall toxins and periodontal stem cell function.

KEYWORDS:

epigenetic regulation; extracellular matrix genes; inflammation; periodontal ligament

PMID:
31218921
DOI:
10.1089/scd.2019.0125

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center