Osteoclasts originated from hematopoietic stem cells are multi-nucleated cells that can resorb the bone matrix. Receptor activator of nuclear factor kappa-B (RANK)/RANK ligand (RANKL) signaling pathway is crucial for the differentiation and activation of osteoclasts. In this study, we investigated for the first time whether or not RANKL induced mitogen- and stress-activated kinase 1 (MSK1) phosphorylation at Ser 376. Activation of MSK1 was detected as soon as 5 min after RANKL stimulation and sparsely detected at 30 min after stimulation. RANKL-induced MSK1 phosphorylation occurred in a dose-dependent manner. MSK1 is known as a downstream signaling molecule of cAMP-dependent protein kinase (PKA). Treatment with the PKA inhibitor H89 significantly suppressed c-Fos and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) induction upon RANKL stimulation. In addition, cAMP response element-binding protein (CREB) phosphorylation was extremely inhibited by H89 treatment. Mitogen-activated protein kinases (MAPKs) have been investigated for induction of MSK1 phosphorylation. Specific signaling pathway inhibitors for p38 and extracellular signal-regulated kinases (ERKs) significantly blocked RANKL-induced MSK1 activation. Finally, as a downstream effector of the p38-MSK1 pathway, c-Fos transcriptional activity was determined. RANKL-mediated elevation of c-Fos transcriptional activity was significantly suppressed by p38 inhibitor. Moreover, a dominant negative form of CREB suppressed activation of NFATc1. In conclusion, RANKL-stimulated MSK1 phosphorylation could play a role in induction of NFATc1 through CREB and c-Fos activation as a downstream molecule of p38, ERK MAPKs, and PKA. Our results support basic information for the development of osteoclast specific inhibitors.

　“reen King”is a new mini kiwifruit variety developed at the National Institute of Subtropical Agriculture (NISA), RDA in 2005, which was an edible fruit without peeling. This variety was selected from seeds obtained from the cross breeding between Actinidia chinensis cv. “pple Sensation”and A. arguta in 1998. Seedling and line selections were conducted from 1999 to 2002, and characteristic trials were carried out from 2003 to 2004. The branch of “reen King”sprouts strongly and the color of leaf is slightly dark green. The shape of fruit is cylindric and the color of peel is green or yellowish green without hair. The average weight of fruit is 15.9 g. The core is small and soft, the pericarp is light green. Soluble solids concentration is 15.4 oBrix. The fruit is sweet with slightly acid taste, containing total acid 1.3%, and the yield is higher over twice than that of A. arguta. The content of vitamin C is higher than that of A. arguta. The harvesting time is from middle October. This variety can be planted in the central and southern region of Korea.