Dental pulp can initiate its damage repair after an injury of the pulp-dentin complex by rearrangement of odontoblasts and formation of newly differentiated odontoblast-like cells. Connexin 43 (Cx43) is one of the gap junction proteins that participates in multiple tissue repair processes. However, the role of Cx43 in the repair of the dental pulp remains unclear. This study aimed to determine the function of Cx43 in the odontoblast arrangement patterns and odontoblastic differentiation. Human teeth for in vitro experiments were acquired, and a pulp injury model in Sprague-Dawley rats was used for in vivo analysis. The odontoblast arrangement pattern and the expression of Cx43 and dentin sialophosphoprotein (DSPP) were assessed. To investigate the function of Cx43 in odontoblastic differentiation, we overexpressed or inhibited Cx43. The results indicated that polarized odontoblasts were arranged along the pulp-dentin interface and had high levels of Cx43 expression in the healthy teeth; however, the odontoblast arrangement pattern was slightly changed concomitant to an increase in the Cx43 expression in the carious teeth. Regularly arranged odontoblast-like cells had high levels of the Cx43 expression during the formation of mature dentin, but the odontoblast-like cells were not regularly arranged beneath immature osteodentin in the pulp injury models. Subsequent in vitro experiments demonstrated that Cx43 is upregulated during odontoblastic differentiation of the dental pulp cells, and inhibition or overexpression of Cx43 influence the odontoblastic differentiation. Thus, Cx43 may be involved in the maintenance of odontoblast arrangement patterns, and influence the pulp repair outcomes by the regulation of odontoblastic differentiation.
Animals ; Cell Differentiation ; Connexin 43 ; Dental Pulp ; Extracellular Matrix Proteins ; Odontoblasts ; Phosphoproteins ; Rats ; Rats, Sprague-Dawley

Objective:To investigate the radiosensitization effect and mechanism of low dose metformin on Hep-G2 tumor bearing mice.Methods:All mice were divided into four groups: control group, radiotherapy group, metformin treatment group and metformin combined with radiotherapy group.After different treatments, the tumor volume of mice in each group was recorded, and the tripling time (TT), tumor growth delay (TGD) and enhancement factor (EF) were calculated.After 21 days, all mice were killed, stripped and weighed, and the tumor inhibition rate was calculated.The effects of different treatments on cell cycle and apoptosis were detected by flow cytometry, and the influences of different treatments on STAT3 signaling pathway and apoptosis related protein expression were detected by immunoblotting.Results:Low dose metformin combined with radiotherapy could significantly inhibit the growth of tumor in mice, and had a better radiosensitization effect, with a sensitization coefficient of 1.52.In addition, the combined treatment group could significantly induce G2/M arrest and apoptosis of Hep-G2 cells[the combined group vs.The radiotherapy group: G2/M phase ratio, (28.4±5.3)% vs.(10.8±3.7)%, t=8.55, P<0.05; apoptosis rate, (28.4±5.3)% vs.(10.8±3.7)%, t=11.83, P<0.01]. Furthermore, compared with the single radiotherapy group, the combined group could significantly reduce the phosphorylation level of STAT3 ( t=10.71, P<0.01), and regulate the expression of apoptosis-related proteins. Conclusion:Metformin has antitumor and radiosensitizing effects on Hep-G2 hepatoma-bearing mice, the mechanism of which may be related to the induction of G2/M phase arrest and the inhibition of STAT3 signaling pathway.