The cancer stem cell (CSC) model is a prominent concept to explain heterogeneity of tumours. 1 CSCs have been revealed to be a self-renewing subpopulation in tumours that generate various differentiated cell populations. Characterization of CSCs has indicated that they are remarkably resistant to conventional radiotherapy and chemotherapy. Clinically, the residual populations of CSCs are
Objectives: Mechanical stimuli are essential for the maintenance of periodontal ligament (PDL) homeostasis. Although there are several studies on atrophic changes in PDL due to occlusal hypofunction, the underlying mechanism is still unknown. Here, we aimed to explore the changes of gene expression in occlusal hypofunctional PDL and elucidate the related role in maintaining the PDL homeostasis.Methods: To investigate the transcriptomic difference between control and hypofunctional PDL tissue from patients, RNA sequencing was performed on 34 human teeth. The atrophic changes in PDL were evaluated by histological analysis. The effect of the Bardet-Biedl syndrome 7 (BBS7) knockdown was evaluated by the RT-qPCR, Western blot, wound healing, and tubule formation assay.Results: We detected that the expression of BBS7 was downregulated in occlusal hypofunctional PDL through RNA sequencing. Dynamic changes, including the number of periodontal ligament cells, alignment of collagen fibers, diameter of blood vessels, appearance of primary cilia, and torturous oxytalan fibers, were observed following occlusal hypofunction. Furthermore, Sonic hedgehog signaling (Shh) activity was closely associated with BBS7 expression in PDL cells. In addition, the cell migration and angiogenesis were also suppressed by BBS7 knockdown in vitro.Conclusion: We suggest that BBS7 plays an essential role in maintaining Shh signaling activity for PDL homeostasis.
Objectives
Runx3, a member of the Runx family of transcription factors, has been studied as a tumour suppressor and key player of organ development. In a previous study, we reported differentiation failure and excessive angiogenesis in the liver of Runx3 knock‐out (KO) mice. Here, we examined a function of the Runx3 in liver, especially in iron metabolism.
Methods
We performed histological and immunohistological analyses of the Runx3 KO mouse liver. RNA‐sequencing analyses were performed on primary hepatocytes isolated from Runx3 conditional KO (cKO) mice. The effect of Runx3 knock‐down (KD) was also investigated using siRNA‐mediated KD in functional human hepatocytes and human hepatocellular carcinoma cells.
Result
We observed an iron‐overloaded liver with decreased expression of hepcidin in Runx3 KO mice. Expression of BMP6, a regulator of hepcidin transcription, and activity of the BMP pathway were decreased in the liver tissue of Runx3 KO mice. Transcriptome analysis on primary hepatocytes isolated from Runx3 cKO mice also revealed that iron‐induced increase in BMP6 was mediated by Runx3. Similar results were observed in Runx3 knock‐down experiments using HepaRG cells and HepG2 cells. Finally, we showed that Runx3 enhanced the activity of the BMP6 promoter by responding to iron stimuli in the hepatocytes.
Conclusion
In conclusion, we suggest that Runx3 plays important roles in iron metabolism of the liver through regulation of BMP signalling.
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