DNA synthesis of rat bone marrow mesenchymal stem cells through alpha1-adrenergic receptors.

Multipotential bone marrow mesenchymal stem cells (BMSCs) are important in maintaining the microenvironment of the bone marrow (BM). Sympathetic nerves histologically innervate the BM; however, their role remains unclear. In this study, the effects of norepinephrine on DNA synthesis and the related signaling molecules involved in rBMSCs were examined. mRNA levels of the alpha1-adrenergic receptor subtypes increased following norepinephrine stimulation (10(-5) M for 30 min). DNA synthesis increased in dose- and time-dependent manners as determined by [(3)H]thymidine incorporation. Intracellular Ca(2+) concentration and translocation of protein kinase C from the cytosol to the membrane were also found to be elevated in rBMSCs. Phentolamine was able to suppress translocation of PKC. Norepinephrine also induced phosphorylation of ERK1/2, which was prevented by staurosporine treatment. Pretreatment with PD98059 inhibited ERK1/2 phosphorylation and DNA synthesis in rBMSCs. These findings indicate that norepinephrine stimulates DNA synthesis via alpha1-adrenergic receptors and downstream Ca(2+)/PKC and ERK1/2 activation in rBMSCs.