RESUMO
TiO2nanotubes (TNTs) significantly promote osteogenic differentiation and bone regeneration of cells. Nevertheless, the biological processes by which they promote osteogenesis are currently poorly understood. Long non-coding RNAs (lncRNAs) are essential for controlling osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Epigenetic chromatin modification is one of the pathways in which lncRNAs regulate osteogenic differentiation. Here, we reported that TNTs could upregulate lncRNARMRP, and inhibition of lncRNARMRPin human BMSCs (hBMSCs) grown on TNTs could decrease runt-related transcription factor 2 (RUNX2), alkaline phosphatase, osteopontin, and osteocalcin (OCN) expression. Furthermore, we discovered that inhibiting lncRNARMRPelevated the expression of lncRNADLEU2, and lncRNADLEU2knockdown promoted osteogenic differentiation in hBMSCs. RNA immunoprecipitation experiments showed that lncRNADLEU2could interact with EZH2 to induce H3K27 methylation in the promoter regions of RUNX2 and OCN, suppressing gene expression epigenetically. According to these results, lncRNARMRPis upregulated by TNTs to promote osteogenic differentiation throughDLEU2/EZH2-mediated epigenetic modifications.
Assuntos
MicroRNAs , Nanotubos , RNA Longo não Codificante , Humanos , Osteogênese/fisiologia , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Epigênese Genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Diferenciação Celular/fisiologia , Células da Medula Óssea , Células Cultivadas , MicroRNAs/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismoRESUMO
Dental mesenchymal stem cells (DMSCs) are crucial in tooth development and periodontal health, and their multipotential differentiation and self-renewal ability play a critical role in tissue engineering and regenerative medicine. Methylation modifications could promote the appropriate biological behavior by postsynthetic modification of DNA or protein and make the organism adapt to developmental and environmental prompts by regulating gene expression without changing the DNA sequence. Methylation modifications involved in DMSC fate include DNA methylation, RNA methylation, and histone modifications, which have been proven to exert a significant effect on the regulation of the fate of DMSCs, such as proliferation, self-renewal, and differentiation potential. Understanding the regulation of methylation modifications on the behavior and the immunoinflammatory responses involved in DMSCs contributes to further study of the mechanism of methylation on tissue regeneration and inflammation. In this review, we briefly summarize the key functions of histone methylation, RNA methylation, and DNA methylation in the differentiation potential and self-renewal of DMSCs as well as the opportunities and challenges for their application in tissue regeneration and disease therapy.
