Journal
STEM CELLS INTERNATIONAL
Volume 2016, Issue -, Pages -Publisher
HINDAWI LTD
DOI: 10.1155/2016/6570671
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Funding
- National Natural Science Foundation of China [31372397]
- Guangdong Special Support Program [2014TQ01N260]
- Research Fund for the Doctoral Program of Higher Education of China [20124404130001]
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Porcine bone marrow mesenchymal stem cells (pBMSCs) have the potential for application in regenerative medicine. This study aims to investigate the effects of extracellular calcium ([Ca2+](o)) on pBMSCs proliferation and to explore the possible underlying mechanisms. The results demonstrated that 4mM [Ca2+](o) significantly promoted pBMSCs proliferation by reducing the G0/G1 phase cell percentage and by increasing the S phase cell proportion and the proliferation index of pBMSCs. Accordingly, [Ca2+](o) stimulated the expression levels of proliferative genes such as cyclin A2, cyclin D1/3, cyclin E2, and PCNA and inhibited the expression of p21. In addition, [Ca2+](o) resulted in a significant elevation of intracellular calcium and an increased ratio of pERK/ERK. However, inhibition of calcium-sensing receptor (CaSR) by its antagonist NPS2143 abolished the aforementioned effects of [Ca2+](o). Moreover, [Ca2+](o)-induced promotion of pBMSCs proliferation, the changes of proliferative genes expression levels, and the activation of ERK1/2 signaling pathway were effectively blocked by U0126, a selective ERK kinase inhibitor. In conclusion, our findings provided evidence that the enhanced pBMSCs proliferation in response to [Ca2+](o) was associated with the activation of CaSR and ERK1/2 signaling pathway, which may be useful for the application of pBMSCs in future clinical studies aimed at tissue regeneration and repair.
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