Circular RNAs (circRNAs) are novel noncoding RNAs and play crucial roles in various biological processes. However, little is known about the functions of circRNAs in osteogenic differentiation. The current study aimed to investigate the differential expression of circRNAs in rat dental follicle cells (rDFCs) during osteogenic differentiation, identified by RNA high-throughput sequencing and quantitative real-time polymerase chain reaction. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to further explore the biofunctions of circRNA biofunctions. Two hundred sixtysix differentially-expressed circRNAs that are involved in several important signaling pathways, including mitogen-activated protein kinases (MAPK) and transforming growth factor-β (TGF-β) signaling pathways were revealed. Among these, circFgfr2 and its predicted downstream targets, miR-133 and BMP6 (bone morphogenetic protein-6), were identified both in vivo and in vitro. For further validation, circFgfr2 was overexpressed in rDFCs, the results showed that the expression of miR-133 was downregulated and the expression of BMP6 was upregulated. Taken together, the results revealed the circRNA expression profiles and indicated the importance of circRNAs of rDFCs. In addition, circFgfr2 might promote osteogenesis by controlling miR-133/BMP6, which is a potential new target for the manipulation of tooth regeneration and bone formation. K E Y W O R D SGene Ontology, high-throughput sequencing, mitogen-activated protein kinase signaling system, microRNAs, osteogenesis

Dental follicle stem/progenitor cells have the potential to undergo osteogenesis. naked cuticle homolog 2 (Nkd2) is a signal-inducible feedback antagonist of the canonical Wnt signaling pathway. The purpose of the present study was to investigate the function of Nkd2 in the differentiation of dental follicle stem/progenitor cells (DFSCs) into osteoblasts. Immunohistochemistry, reverse transcription-quantitative polymerase chain reaction and western blotting were employed to detect Nkd2 expression in rat DFSCs. In addition, rat DFSCs (rDFSCs) were transfected with small interfering RNAs to examine the effect of Nkd2 on the differentiation of these cells into osteoblasts. Furthermore, the function of Nkd2 in the Wnt/β-catenin pathway in rDFSCs was investigated using β-catenin/T-cell factor luciferase activity assays and western blotting. It was revealed that the expression of Nkd2 was upregulated during the differentiation of rDFSCs into osteoblasts. Furthermore, osteoblast differentiation ability and Wnt/β-catenin pathway activity were significantly decreased in Nkd2-silenced rDFSCs compared with the si-NC group (P<0.05 and P<0.001, respectively). The results suggest that Nkd2 promotes the differentiation of rDFSCs into osteoblasts through Wnt/β-catenin signaling.

Erythropoietin (EPO) is a 34-kDa glycoprotein that possesses the potential for angiogenesis, as well as antiinflammatory and anti-apoptotic properties. The present study aimed to examine the effect of EPO on the angiogenesis of dental pulp cells (DPCs) and to explore the underlying mechanisms of these effects. It was demonstrated that EPO not only promoted DPCs proliferation but also induced angiogenesis of DPCs in a paracrine fashion. EPO enhanced the angiogenic capacity by stimulating DPCs to secrete a series of angiogenic cytokines. ELISA confirmed that high concentrations of EPO increased the production of MMP-3 and angiopoietin-1 but decreased the secretion of IL-6. Furthermore, EPO activated the ERK1/2 and p38 signaling pathways in DPCs, while inhibition of these pathways diminished the angiogenesis capacity of DPCs. The present study suggested that EPO may have an important role in the repair and regeneration of dental pulp.

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Sirtuins (SIRTs 1-7) are a group of histone deacetylase enzymes with a wide range of enzyme activities that target a range of cellular proteins in the nucleus, cytoplasm, and mitochondria for posttranslational modifications by acetylation (SIRT1, 2, 3, and 5) or ADP ribosylation (SIRT4, 6, and 7). A variety of cellular functions, including mitochondrial functions and functions in energy homeostasis, metabolism, cancer, longevity and ageing, are regulated by sirtuins. Compromised sirtuin functions and/or alterations in the expression levels of sirtuins may lead to several pathological conditions and contribute significantly to alterations in metabolic phenotypes as well as oral carcinogenesis. Here, we describe the basic characteristics of seven mammalian sirtuins. This review also emphasizes the key molecular mechanisms of sirtuins in metabolic regulation and discusses the possible relationships of sirtuins with oral cancers. This review will provide novel insight into new therapeutic approaches targeting sirtuins that may potentially lead to effective strategies for combating oral malignancies.