Abstract
ABSTRACTThe present study investigated the cellular properties in the dental tissue-derived mesenchymal stem cells (DSCs) exposed to nevirapine (NVP), an inhibitor of reverse transcriptase (RTase). After a prolonged exposure of DSCs for 2 weeks, the population doubling time (PDT) was significantly (P < .05) increased by delayed cell growth in the DSCs treated with 250 and 500 μM NVP, compared with untreated DSCs. Furthermore, the G1 phase of cell cycle with high activity of senescence-associated β-galactosidase was also significantly (P < .05) increased in the 250 μM NVP-treated DSCs, compared with untreated DSCs. The level of telomerase activity was unchanged between control and treatment. However, following the treatment of NVP, negative surface markers for mesenchymal stem cells (MSCs), such as CD34 and CD45, were significantly (P < .05) increased, while positive surface markers for MSCs, such as CD90 and CD105, were significantly (P < .05) decreased in the NVP-treated DSCs than those of untreated DSCs. Furthermore, the differentiation capacity into mesodermal lineage was gradually decreased, and a significant (P < .05) decrease of expression level of NANOG, OCT-4 and SOX-2 transcripts was observed in the DSCs treated with NVP, compared with untreated control DSCs. Taken together, the present results have revealed that inhibition of RTase by NVP induces delayed cell growth and loss of stemness.
Highlights
1.5% of human genome with 23 chromosome pairs is only covered with coding sequences that can be translated to proteins
The population doubling time (PDT) in untreated control derived mesenchymal stem cells (DSCs), DSCs supplemented with 0.5% dimethyl sulfoxide (DMSO), DSCs treated with 100 μM NVP, DSCs treated with 250 μM NVP and DSCs treated with 500 μM NVP were 39.2 ± 5.34, 40.1 ± 3.68, 41.7.0 ± 8.23, 59.3 ± 7.79 and 92.7 ± 10.51, respectively
The mesenchymal stem cells (MSCs) derived from dental tissues of wisdom teeth (DSCs) were exposed to nevirapine (NVP) which is commonly used as an antiretroviral drug via inhibition of reverse transcriptase (RTase), for up to 2 weeks
Summary
1.5% of human genome with 23 chromosome pairs is only covered with coding sequences that can be translated to proteins. The largest component (∼45%) in the non-coding sequences of the genome is transposable elements (TEs), including Class I (retrotransposons) and Class II (DNA transposons), and most of the TEs are Class I retrotransposons (Mills et al 2007; Lander 2011). A part of the Class II DNA transposons is severed and transposed at new position of the genome, as ‘cut and paste’ mechanism, while a part of Class I retrotransposons is copied to RNA intermediate, converted into DNA by the activity of a reverse transcriptase (RTase) and transposed, as ‘copy and paste’ mechanism (Magiorkinis et al 2017). Retroviruses are mostly RNA viruses that convert their RNA genome into the DNA intermediate using their RTase activity (Preston et al 1988).
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