The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

SC-19220, antagonist of prostaglandin E2 receptor EP1, inhibits osteoclastogenesis by RANKL.

We examined the direct effect of SC-19220, an EP1 prostaglandin (PG) E2 receptor antagonist, on osteoclastogenesis induced by RANK/RANKL signaling in mouse cell cultures. We found that SC-19220 inhibited RANKL-induced osteoclastogenesis by suppression of the RANK/RANKL signaling pathway in osteoclast precursors. INTRODUCTION: Bone growth is accomplished by a dynamic equilibrium between formation by osteoblasts and resorption by osteoclasts, which are regulated by many systemic and local osteotropic factors that induce osteoclast formation from hematopoietic precursors through RANK/RANKL signaling. There are four subtypes of prostaglandin E (PGE) receptors, EP1, EP2, EP3, and EP4, and PGE2 facilitates bone resorption by a mechanism mediated by EP2/EP4. It is well known that SC-19220 is an EP1-specific antagonist. We previously found that SC-19220 inhibited osteoclastogenesis induced by osteotropic factors, including PGE2; however, the inhibitory mechanism is not clear. In this study, we investigated the inhibitory effects of SC-19220 on osteoclastogenesis induced by RANK/RANKL signaling in mouse cell cultures and analyzed the mechanism involved. MATERIALS AND METHODS: A bone marrow culture system and bone marrow macrophages were used to examine the effects of SC-19220 on PGE2-, 11-deoxy-PGE1-, and RANKL-induced osteoclastogenesis. We analyzed RANKL expression in osteoblasts induced by PGE2 using RT-PCR. We also examined the effects of SC-19220 on the macrophage-colony-stimulating factor (M-CSF) receptor (c-Fms) and RANK expression in osteoclast precursors as well as RANK/RANKL signaling using RT-PCR and Western blotting analyses. RESULTS AND CONCLUSION: SC-19220 dose-dependently inhibited osteoclast formation induced by PGE2, 11-deoxy-PGE1, and RANKL in the mouse culture system; however, it had no influence on RANKL expression in osteoblasts induced by PGE2. Furthermore, the expression of RANK and c-Fms in osteoclast precursors was decreased by SC-19220 at the mRNA and protein levels. In RANK signaling networks, SC-19220 inhibited c-Src and NFAT2 expression. Our findings indicated that SC-19220 inhibits RANKL-induced osteoclastogenesis through the suppression of RANK, c-Fms, c-Src, and NFAT2, suggesting that this EP1-specific antagonist inhibits osteoclast formation induced by RANKL from the early stage of osteoclastogenesis.[1]


  1. SC-19220, antagonist of prostaglandin E2 receptor EP1, inhibits osteoclastogenesis by RANKL. Tsujisawa, T., Inoue, H., Nishihara, T. J. Bone Miner. Res. (2005) [Pubmed]
WikiGenes - Universities