L-type voltage-dependent Ca(2+) channels (VDCC(L)) play an important role in the maintenance of intracellular calcium homeostasis, and influence multiple cellular processes. They have been confirmed to contribute to the functional activities of osteoblasts. Recently, VDCC(L) expression was reported in mesenchymal stem cells (MSCs), but the role of VDCC(L) in MSCs is still undetermined. The aim of this study was to determine whether VDCC(L) may be regarded as a new regulator in the proliferation and osteogenic differentiation of rat MSC (rMSCs). In this study, we examined functional Ca(2+) currents (I(Ca)) and mRNA expression of VDCC(L) in rMSCs, and then suppressed VDCC(L) using nifedipine (Nif), a VDCC(L) blocker, to investigate its role in rMSCs. The proliferation and osteogenic differentiation of MSCs were analyzed by MTT, flow cytometry, alkaline phosphatase (ALP), Alizarin Red S staining, RT-PCR, and real-time PCR assays. We found that Nif exerts antiproliferative and apoptosis-inducing effects on rMSCs. ALP activity and mineralized nodules were significantly decreased after Nif treatment. Moreover, the mRNA levels of the osteogenic markers, osteocalcin (OCN), bone sialoprotein (BSP), and runt-related transcription factor 2 (Runx2), were also down-regulated. In addition, we transfected α1C-siRNA into the cells to further confirm the role of VDCC(L) in rMSCs, and a similar effect on osteogenesis was found. These results suggest that VDCC(L) plays a crucial role in the proliferation and osteogenic differentiation of rMSCs.
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