Long non-coding RNA H19/SAHH axis epigenetically regulates odontogenic differentiation of human dental pulp stem cells

• Published in: Cellular signalling Vol. 52; pp. 65 - 73
• Main Authors: Zeng, Li, Sun, Shichen, Han, Dong, Liu, Yang, Liu, Haochen, Feng, Hailan, Wang, Yixiang
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01-12-2018
• Subjects: Adenosylhomocysteinase - genetics; Cell Differentiation - genetics; Cells, Cultured; Dental Pulp - cytology; DNA (Cytosine-5-)-Methyltransferases - metabolism; DNA Methyltransferase 3B; Epigenesis, Genetic; Epigenetic regulation; H19/SAHH; hDPSCs; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Humans; Odontogenesis - genetics; Odontogenic differentiation; RNA, Long Noncoding - genetics; RNA, Long Noncoding - physiology; Stem Cells - cytology; Stem Cells - metabolism; Transcription Factors - genetics; Transcription Factors - metabolism; H19/SAHH; Epigenetic regulation; hDPSCs; Odontogenic differentiation
• ISSN: 0898-6568; 1873-3913
• DOI: 10.1016/j.cellsig.2018.08.015

Long noncoding RNAs (lncRNAs) are emerging as important regulators in molecular processes and may play vital roles in odontogenic differentiation of human dental pulp stem cells (hDPSCs). However, their functions remain to be elucidated. As lncRNA H19 is one of the most classical lncRNA, which plays essential roles in cellular differentiation, thus we explored the effects and mechanisms of H19 in odontogenic differentiation of hDPSCs. Stable overexpression and knockdown of H19 in hDPSCs were constructed using recombinant lentiviruses containing H19 and short hairpin-H19 expression cassettes, respectively. Alkaline phosphatase (ALP) assay, Alizarin red staining assay, von kossa staining, quantitative polymerase chain reaction (qPCR), Western blot analysis, and immunofluorescent staining results indicated that overexpression of H19 in hDPSCs positively regulates the odontogenic differentiation of hDPSCs, while knockdown of H19 in hDPSCs inhibits odontogenic differentiation of hDPSCs. Further, we found that H19 promotes the odontogenic differentiation of hDPSCs through S-adenosylhomocysteine hydrolase (SAHH) epigenetically regulates the methylation and expression of distal-less homeobox (DLX3) gene. Herein, for the first time, we determined that H19/SAHH axis epigentically regulates odontogenic differentiaiton of hDPSCs by inhibiting the DNA methyltransferase 3B (DNMT3B)-mediated methylation of DLX3. Our findings provide a new insight into how H19/SAHH axis play its role in odontogenic differentiation of hDPSCs, and would be helpful in developing therapeutic approaches for dentin regeneration based on stem cells.
•Long non-coding RNA H19 is emerging as an important molecular in cellular differentiation. However, its role in odontogenic differentiation of hDPSCs is still unknown.•Long non-coding RNA H19 promotes the odontogenic differentiation of hDPSCs.•The inhibition of SAHH activity by H19 results in a decreased activity of DNMT3B.•Long non-coding RNA H19 facilitates odontogenic differentiation of hDPSCs via H19/SAHH axis epigenetically regulates DLX3.