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Our previous study has showed that co-grafted Schwann cells (SCs) promote proliferation and migration of the grafted oligodendrocyte precursor cells (OPCs). However, how the co-grafted SCs affect OPCs has not been clarified. In the present study, we confirmed that SC-induced proliferation and migration of OPCs were mediated by SC-secreted factors using SC-conditioned medium (SCM). Then, we detected several candidate factors, PDGF-AA, FGF-2, and IGF-1, in SCs and SCM, and their receptors in OPCs. Finally, by using the selective inhibitors, the effects of these candidate factors on proliferation and migration of OPCs were examined. Our results showed that SCM-stimulated proliferation and migration of OPCs could be markedly decreased by both AG1295 (the inhibitor of PDGFR) and PD173074 (the inhibitor of FGFR). Together, our study suggests that SCs affect proliferation and migration of OPCs through secreting PDGF-AA and FGF-2. Identity of these molecules not only contributes to understand the mechanism of SC-induced proliferation and migration of OPCs but also provides possible target for treatment of CNS diseases. [ABSTRACT FROM AUTHOR]

The conditioned medium from B104 neuroblastoma cells (B104CM) induces proliferation of oligodendrocyte progenitor cells (OPCs) in vitro. Our previous study showed that phosphorylation of extracellular signal-regulated protein kinase(s), not PI3K or p38, is key to B104CM-induced OPC proliferation. However, whether there are still other signaling pathways that are also involved in B104CM-induced proliferation remains unknown. In the present study, we evaluated the implication of c-Jun N-terminal kinase (JNK) signaling pathway in the B104CM-induced proliferation of OPCs using the specific inhibitor of JNK. We provided convincing evidence for the first time that the phosphorylation of JNK is necessary for OPC proliferation induced by B104CM in vitro. Moreover, the activation of JNK results in subsequent expressions of c-jun, c-fos, and c-myc, which initiates proliferation of OPCs. Collectively, these results suggest that JNK is also necessary for B104CM-induced OPC proliferation. [ABSTRACT FROM AUTHOR]