MiR-21/STAT3 Signal Is Involved in Odontoblast Differentiation of Human Dental Pulp Stem Cells Mediated by TNF-α.
Dental pulp stem cells (DPSCs), as one type of mesenchymal stem cells (MSCs), have the capability of self-renewal and multipotency to differentiate into several cell lineages, including osteogenesis, odontoblasts, chondrogenesis, neurogenesis, and adipogenesis. It has found that tumor necrosis factor-α (TNF-α) can promote osteogenic differentiation of human DPSCs in our previous studies. Other experimentation revealed that signal transducer and activator of transcription 3 (STAT3) underwent a rapid activation both in osteogenesis and inflammation microenvironment of MSCs in vitro. MicroRNAs (miRNAs or miRs) have been proved in previous studies to regulate MSCs differentiation in vitro. In this study, we identified miR-21 as a key miRNA contributed the functional axis of odontoblast differentiation induced by STAT3. It is observed that the expression of miR-21 and STAT3 increased gradually in low concentration (1-10 ng/mL) of TNF-α, while they were suppressed in high concentration (50-100 ng/mL). The upregulation of miR-21 may facilitate the odontoblast differentiation of DPSCs coordinating with STAT3. SiSTAT3 or treated by the inhibitor of STAT3, cucurbitacin I (Cuc I), significantly increased primary miR-21 expression along with decreased mature miR-21 expression. Meanwhile, the inhibition of miR-21 (anti-miR-21) decreased the activation of STAT3 as well as suppressed the marker proteins of odontoblast differentiation. The results revealed a new function of miR-21, suggesting that miR-21/STAT3 signal may act as a modulator within a complex network of factors to regulate odontoblast differentiation of human DPSCs. It may provide a novel therapeutic strategy to regulate the odontoblast differentiation of DPSCs.
['Xu|Ke|K|', 'Xiao|Jingwen|J|', 'Zheng|Ke|K|', 'Feng|Xingmei|X|', 'Zhang|Jinlong|J|', 'Song|Donghui|D|', 'Wang|Chenfei|C|', 'Shen|Xiang|X|', 'Zhao|Xin|X|', 'Wei|Changbo|C|', 'Huang|Dan|D|', 'Feng|Guijuan|G|']
D000293:Adolescent D000328:Adult D002454:Cell Differentiation D002478:Cells, Cultured D003782:Dental Pulp D006801:Humans D035683:MicroRNAs D009804:Odontoblasts D010012:Osteogenesis D050796:STAT3 Transcription Factor D015398:Signal Transduction D013234:Stem Cells D014409:Tumor Necrosis Factor-alpha D055815:Young Adult
miR-21 STAT3 odontoblast differentiation dental pulp stem cells TNF-α