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FAM96B inhibits the senescence of dental pulp stem cells
- Source :
- Cell biology internationalReferences. 44(5)
- Publication Year :
- 2019
-
Abstract
- Dental pulp stem cells (DPSCs) are considered a remarkable source for the regeneration of dental pulp tissues, but their therapeutic effectiveness remains limited, especially in elderly people. Previous studies found that senescence has a negative effect on the proliferation and differentiation potential of DPSCs. Moreover, numerous long non-coding RNA (lncRNA) and messenger RNA were significantly differentially regulated in DPSCs from young and elderly donors. However, the changes in DPSCs protein during senescence have not been addressed. In this study, differences in DPSC protein expression profiles and coexpression of protein and lncRNA were analyzed using proteomics and bioinformatics. The results showed 75 upregulated proteins and 69 downregulated proteins in DPSCs from elderly donors. Vasopressin-regulated water reabsorption, Parkinson's disease, Alzheimer's disease, and protein export were the top four functional pathways associated with DPSCs. High mobility group N1 (HMGN1), HMGN2, UCHL1, and the family with sequence similarity 96 member B homeobox gene (FAM96B) were associated with DPSCs senescence. Then, we investigated FAM96B function in DPSCs. After FAM96B depletion, telomerase reverse transcriptase (TERT) activity decreased, but the number of senescence-associated β-galactosidase (SA-β-gal) positive cells and the protein levels of p16, p53 were significantly increased. Gain-of-function assays suggested that FAM96B overexpression was positively correlated with TERT activity, but negatively correlated with the number of SA-β-gal positive cells and the protein levels of P16 and P53. Moreover, after FAM96B overexpression, the results showed a significant increase in alkaline phosphatase activity and an enhanced mineralization ability of DPSCs. The reverse-transcription polymerase chain reaction results also showed that dentin sialophosphoprotein and osteocalcin were expressed at greater levels. The carboxyfluorescein succinimidyl ester (CFSE) results displayed that FAM96B increased the proliferation potential of DPSCs. Our study revealed candidate proteins that might be related to DPSCs senescence and provided information to elucidate the mechanism of the biological changes in DPSCs' aging. Moreover, FAM96B was demonstrated to play an important role in suppressing DPSCs senescence and promoting osteogenic differentiation and proliferation.
- Subjects :
- 0301 basic medicine
Senescence
HMGN1
Adult
HMGN2
Aging
03 medical and health sciences
chemistry.chemical_compound
Young Adult
0302 clinical medicine
stomatognathic system
Dentin sialophosphoprotein
Osteogenesis
Dental pulp stem cells
Metalloproteins
Humans
Telomerase reverse transcriptase
Cells, Cultured
Cellular Senescence
Dental Pulp
Aged
Cell Proliferation
biology
Stem Cells
Nuclear Proteins
Carboxyfluorescein succinimidyl ester
Cell Differentiation
Cell Biology
General Medicine
Middle Aged
Healthy Volunteers
Cell biology
030104 developmental biology
chemistry
030220 oncology & carcinogenesis
Osteocalcin
biology.protein
Subjects
Details
- ISSN :
- 10958355
- Volume :
- 44
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Cell biology internationalReferences
- Accession number :
- edsair.doi.dedup.....720f790753875ce15a32d438512240a4