Repeated stimulation by LPS promotes the senescence of DPSCs via TLR4/MyD88-NF-κB-p53/p21 signaling.
Guijuan FengKe ZhengTong CaoJinlong ZhangMin LianDan HuangChangbo WeiZhifeng GuXingmei FengPublished in: Cytotechnology (2018)
Dental pulp stem cells (DPSCs), one type of mesenchymal stem cells, are considered to be a type of tool cells for regenerative medicine and tissue engineering. Our previous studies found that the stimulation with lipopolysaccharide (LPS) might introduce senescence of DPSCs, and this senescence would have a positive correlation with the concentration of LPS. The β-galactosidase (SA-β-gal) staining was used to evaluate the senescence of DPSCs and immunofluorescence to show the morphology of DPSCs. Our findings suggested that the activity of SA-β-gal has increased after repeated stimulation with LPS and the morphology of DPSCs has changed with the stimulation with LPS. We also found that LPS bound to the Toll-like receptor 4 (TLR4)/myeloid differentiation factor (MyD) 88 signaling pathway. Protein and mRNA expression of TLR4, MyD88 were enhanced in DPSCs with LPS stimulation, resulting in the activation of nuclear factor-κB (NF-κB) signaling, which exhibited the expression of p65 improved in the nucleus while the decreasing of IκB-α. Simultaneously, the expression of p53 and p21, the downstream proteins of the NF-κB signaling, has increased. In summary, DPSCs tend to undergo senescence after repeated stimulation in an inflammatory microenvironment. Ultimately, these findings may lead to a new direction for cell-based therapy in oral diseases and other regenerative medicines.
Keyphrases
- umbilical cord
- toll like receptor
- inflammatory response
- mesenchymal stem cells
- nuclear factor
- lps induced
- stem cells
- signaling pathway
- cell therapy
- dna damage
- endothelial cells
- anti inflammatory
- tissue engineering
- induced apoptosis
- immune response
- stress induced
- poor prognosis
- pi k akt
- oxidative stress
- cell cycle arrest
- acute myeloid leukemia
- endoplasmic reticulum stress
- single cell
- protein protein
- small molecule
- amino acid