Evidence of The Correlation Between Wnt Signaling and The Expression of Telomerase Components in the Human Mesenchymal Stem Cells Derived from Peripheral Blood

Background and Aim: Telomerase activity has been known to play acritical role in the remaining proliferation potential of stem cells includingmesenchymal stem cells (MSCs). The low number of these cells limitedthe application of these cells in the regenerative medicine and treatmentof diseases. To more understand the molecular mechanisms involvingin the replicative potential of MSCs, the expression of telomerasecomponents and the Wnt signaling pathway was evaluated in the earlyculture as well as the late culture of MSCs.Methods: The mononuclear cells containing MSCs were separated fromperipheral blood using a Ficoll density gradient. After reaching to 70%-80% confluence, the expression of hTERT, hTERC, TCF4, CTNNB1(β-catenin) and GSK were evaluated by Real-time PCR in early culture (8-9th days) and late culture (14th-17th days) of MSCs as compared with thecontrol group (6th days of MSCs culture).Results: Our data indicated that there was a negative correlation betweenGSK and telomerase RNA component (TERC) in the early culture of MSCs(t-test; -2.29, P <0.05). Furthermore, the decrease of the mean expressionof TERT and TERC in late culture was accompanied by the diminishedexpression of TCF4 and the enhanced expression of GSK as comparedwith the early culture of MSCs.Conclusion: The diminished expression of TCF4, as well as the enhancedexpression of GSK, suggested that the inhibition of Wnt signalingpathway plays a role in the decreased expression of human telomerasereverse transcriptase (hTERT) and TERC in the late culture of MSCs. The obtained results could be contributed to the identification of mechanismsinvolving in the maintenance of telomere length and the proliferationpotential of MSCs.

کلیدواژه ها:

Telomerase ، Wnt signaling pathway ، Mesenchymal stem cells ، Cellular senescence