BackgroundDental pulp stem cells (DPSCs) can be driven into odontoblast, osteoblast, and chondrocyte lineages in different inductive media. However, the differentiation potential of naive DPSCs after serial passaging in the routine culture system has not been fully elucidated.ResultsDPSCs were isolated from human/rat dental pulps by the magnetic activated cell sorting based on STRO-1 expression, cultured and passaged in the conventional culture media. The biological features of STRO-1+ DPSCs at the 1st and 9th passages were investigated. During the long-term passage, the proliferation ability of human STRO-1+ DPSCs was downregulated as indicated by the growth kinetics. When compared with STRO-1+ DPSCs at the 1st passage (DPSC-P1), the expression of mature osteoblast-specific genes/proteins (alkaline phosphatase, bone sialoprotein, osterix, and osteopontin), odontoblast-specific gene/protein (dentin sialophosphoprotein and dentin sialoprotein), and chondrocyte-specific gene/protein (type II collagen) was significantly upregulated in human STRO-1+ DPSCs at the 9th passage (DPSC-P9). Furthermore, human DPSC-P9 cells in the mineralization-inducing media presented higher levels of alkaline phosphatase at day 3 and day 7 respectively, and produced more mineralized matrix than DPSC-P9 cells at day 14. In vivo transplantation results showed that rat DPSC-P1 cell pellets developed into dentin, bone and cartilage structures respectively, while DPSC-P9 cells can only generate bone tissues.ConclusionsThese findings suggest that STRO-1+ DPSCs consist of several interrelated subpopulations which can spontaneously differentiate into odontoblasts, osteoblasts, and chondrocytes. The differentiation capacity of these DPSCs changes during cell passaging, and DPSCs at the 9th passage restrict their differentiation potential to the osteoblast lineage in vivo.

Background information. Although adult bone-marrow-derived cell populations have been used to make teeth when recombined with embryonic oral epithelium, the differences between dental and non-dental stem-cell-mediated odontogenesis remain an open question.Results. STRO-1 + (stromal precursor cell marker) DPSCs (dental pulp stem cells) and BMSSCs (bone marrow stromal stem cells) were isolated from rat dental pulp and bone marrow respectively by magnetic-activated cellsorting techniques. Their odontogenic capacity was compared under the same inductive microenvironment produced by ABCs (apical bud cells) from 2-day-old rat incisors. Co-cultured DPSCs/ABCs in vitro showed more active odontogenic differentiation ability than mixed BMSSCs/ABCs, as indicated by the accelerated matrix mineralization, up-regulated alkaline phosphatase activity, cell-cycle modification, and the expression of tooth-specific proteins and genes. After cultured for 14 days in the renal capsules of rat hosts, recombined DPSC/ABC pellets formed typical tooth-shaped tissues with balanced amelogenesis and dentinogenesis, whereas BMSSC/ABC recombinants developed into atypical dentin-pulp complexes without enamel formation. DPSC and BMSSC pellets in vivo produced osteodentin-like structures and fibrous connective tissues respectively.Conclusions. DPSCs presented more striking odontogenic capability than BMSSCs under the induction of postnatal ABCs. This report provides critical insights into the selection of candidate cells for tooth regeneration between dental and non-dental stem cell populations.

Two crucial growth factors, FGF2 and TGFbeta1, were investigated in this study to determine their inductive effects on the odontoblastic differentiation of human dental pulp stem cells (DPSCs) in vitro. DPSCs were isolated by immunomagnetic bead selection using the STRO-1 antibody, and then co-cultured respectively with FGF2, TGFbeta1 and FGF2+TGFbeta1. The results showed that FGF2 can exert a significant effect on the cell proliferation, while TGFbeta1 or FGF2+TGFbeta1 can initiate an odontoblast-like differentiation of DPSCs. Moreover, FGF2 can synergistically upregulate the effects of TGFbeta1 on the odontoblastic differentiation of DPSCs, as indicated by the increased alkaline phosphatase activity, the polarized cell appearance and secretary ultrastructural features, the formation of mineralized nodules and the gene/protein expression of dentin sialoprotein and dentin matrix protein-1. Together, FGF2 acted primarily on the cell proliferation, while TGFbeta1 and FGF2+TGFbeta1 mainly stimulated the odontoblastic differentiation of DPSCs. This study provides interesting progress in the odontoblastic differentiation of DPSCs induced by FGF2 and TGFbeta1.

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Abstract. Lung cancer is one of the leading causes of cancerrelated death worldwide. Curcumin has been reported to have an antitumor effect by inducing apoptosis and suppressing growth of tumor cells. However, the mechanism by which curcumin exerts its anti-cancer effect needs further research. The purpose of the present study was to identify a miRNAmediated mechanism which plays a role in the anti-cancer effects of curcumin. Alterations in miRNA expression were seen in curcumin-treated A549 cells, including significant downregulation of miRNA-186 * expression by microarray analysis and real-time PCR. The miRNA-186 * functions by overexpression or inhibition were investigated using biological assays in A549 cells. Additionally, caspase-10 was identified as a target of miRNA-186 * using dual luciferase reporter assays and Western blot analysis. These results demonstrate that curcumin induces A549 cell apoptosis through a miRNA pathway. Also, miRNA-186 * could serve as a potential gene therapy target in curcumin treatment. Furthermore, caspase-10 was shown to be a target of miR-186 * regulation.

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Investigations of the odontoblast phenotype are hindered by obstacles such as the limited number of odontoblasts within the dental pulp and the difficulty in purification of these cells. Therefore, it is necessary to develop a cell culture system in which the local environment is inductive and can promote dental pulp stem cells (DPSCs) to differentiate into odontoblast lineage. In this study, we investigated the effect of conditioned medium from developing tooth germ cells (TGCs) on the differentiation and dentinogenesis of DPSCs both in vitro and in vivo. DPSCs were enzymatically isolated from the lower incisors of 4-week-old Sprague-Dawley rats and co-cultured with TGC conditioned medium (TGC-CM). The cell phenotype of induced DPSCs presents many features of odontoblasts, as assessed by the morphologic appearance, cell cycle modification, increased alkaline phosphatase level, synthesis of dentin sialoprotein, type I collagen and several other noncollagenous proteins, expression of the dentin sialophosphoprotein and dentin matrix protein 1 genes, and the formation of mineralized nodules in vitro. The induced DPSC pellets in vivo generated a regular-shaped dentin-pulp complex containing distinct dentinal tubules and predentin, while untreated pellets spontaneously differentiated into bone-like tissues. To our knowledge, this is the first study to mimic the dentinogenic microenvironment from TGCs in vitro, and our data suggest that TGC-CM creates the most odontogenic microenvironment, a feature essential and effective for the regular dentinogenesis mediated by DPSCs.

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