Histone demethylase KDM5A regulates the functions of human periodontal ligament stem cells during periodontitis via the miR-495-3p/HOXC8 axis.
Histone demethylase
KDM5A
Periodontitis
Stem cell function
hPDLSCs
miR-495-3p
Journal
Regenerative therapy
ISSN: 2352-3204
Titre abrégé: Regen Ther
Pays: Netherlands
ID NLM: 101709085
Informations de publication
Date de publication:
Jun 2022
Jun 2022
Historique:
received:
18
10
2021
revised:
01
12
2021
accepted:
15
12
2021
entrez:
5
5
2022
pubmed:
6
5
2022
medline:
6
5
2022
Statut:
epublish
Résumé
Periodontitis is the sixth most common human disease and epigenetic regulation is identified to affect the functions of stem cells. This research aims to analyze the role of histone demethylase Lysine-specific demethylase 5A (KDM5A) in human periodontal ligament stem cells (hPDLSCs) with periodontitis. hPDLSCs were treated with porphyromonas gingivalis-lipopolysaccharide (Pg-LPS) and subjected to osteogenic induction. The expression of KDM5A was detected by RT-qPCR and Western blot. Then, KDM5A expression patterns in hPDLSCs were measured and then silenced using shRNA to explore its role in osteogenic differentiation (OD), proliferation, and migration of hPDLSCs. ChIP assay was used to analyze the relationship between KDM5A and miR-495-3p, Western blot was used to detect H3K4me3 and RT-qPCR was used to detect miR-495-3p expression. CPI-455 (specific KDM5 inhibitor) was adopted to confirm the role of H3K4me3, and dual-Luciferase assay indicted the relationship between miR-495-3p and homeobox C8 (HOXC8). A functional rescue experiment was designed to analyze the role of miR-495-3p in hPDLSCs with periodontitis. KDM5A was highly expressed in LPS-treated hPDLSCs. Downregulation of KDM5A promoted OD, proliferation, and migration of hPDLSCs. Mechanically, KDM5A inhibited miR-495-3p expression by demethylation of H3K4me3 to enhance HOXC8 transcription. Downregulation of miR-495-3p could weaken the effect of sh-KDM5A to promote OD, proliferation, and migration of hPDLSCs. KDM5A could bind to the miR-495-3p promoter and inhibit miR-495-3p expression by demethylation of H3K4me3 to enhance HOXC8 transcription, thereby increasing the HOXC8 and limiting OD, proliferation, and migration of hPDLSCs with periodontitis.
Identifiants
pubmed: 35509266
doi: 10.1016/j.reth.2021.12.002
pii: S2352-3204(21)00099-7
pmc: PMC9046131
doi:
Types de publication
Journal Article
Langues
eng
Pagination
95-106Informations de copyright
© 2022 The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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