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DNA Methylation Profiling in Chondrocyte Dedifferentiation In Vitro
- Source :
- Journal of cellular physiology. 232(7)
- Publication Year :
- 2015
-
Abstract
- DNA methylation has emerged as a crucial regulator of chondrocyte dedifferentiation, which severely compromises the outcome of autologous chondrocyte implantation (ACI) treatment for cartilage defects. However, the full-scale DNA methylation profiling in chondrocyte dedifferentiation remains to be determined. Here, we performed a genome-wide DNA methylation profiling of dedifferentiated chondrocytes in monolayer culture and chondrocytes treated with DNA methylation inhibitor 5-azacytidine (5-AzaC). This research revealed that the general methylation level of CpG was increased while the COL-1A1 promoter methylation level was decreased during the chondrocyte dedifferentiation. 5-AzaC could reduce general methylation levels and reverse the chondrocyte dedifferentiation. Surprisingly, the DNA methylation level of COL-1A1 promoter was increased after 5-AzaC treatment. The COL-1A1 expression level was increased while that of SOX-9 was decreased during the chondrocyte dedifferentiation. 5-AzaC treatment up-regulated the SOX-9 expression while down-regulated the COL-1A1 promoter activity and gene expression. Taken together, these results suggested that differential regulation of the DNA methylation level of cartilage-specific genes might contribute to the chondrocyte dedifferentiation. Thus, the epigenetic manipulation of these genes could be a potential strategy to counteract the chondrocyte dedifferentiation accompanying in vitro propagation. J. Cell. Physiol. 232: 1708-1716, 2017. © 2016 Wiley Periodicals, Inc.
- Subjects :
- Adult
Male
Gene Expression Profiling
Down-Regulation
Cell Differentiation
SOX9 Transcription Factor
Cell Dedifferentiation
DNA Methylation
Collagen Type I
Up-Regulation
Phosphatidylinositol 3-Kinases
Chondrocytes
Gene Ontology
Phenotype
Azacitidine
Humans
CpG Islands
Female
Proto-Oncogene Proteins c-akt
Signal Transduction
Subjects
Details
- ISSN :
- 10974652
- Volume :
- 232
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- Journal of cellular physiology
- Accession number :
- edsair.pmid..........a2fde5134e7664c5ce1ec21d1ce725bf