. . . . . "24" . "2006-12-13" . "Sphingosine 1-phosphate (S1P), produced by sphingosine kinase (SPHK), acts both by intracellular and extracellular modes. We evaluated the role of SPHK1 and S1P in osteoclastogenesis using bone marrow-derived macrophage (BMM) single and BMM/osteoblast coculture systems. In BMM single cultures, the osteoclastogenic factor receptor activator of NF-kappaB ligand (RANKL) upregulated SPHK1 and increased S1P production and secretion. SPHK1 siRNA enhanced and SPHK1 overexpression attenuated osteoclastogenesis via modulation of p38 and ERK activities, and NFATc1 and c-Fos levels. Extracellular S1P had no effect in these cultures. These data suggest that intracellular S1P produced in response to RANKL forms a negative feedback loop in BMM single cultures. In contrast, S1P addition to BMM/osteoblast cocultures greatly increased osteoclastogenesis by increasing RANKL in osteoblasts via cyclooxygenase-2 and PGE(2) regulation. S1P also stimulated osteoblast migration and survival. The RANKL elevation and chemotactic effects were also observed with T cells. These results indicate that secreted S1P attracts and acts on osteoblasts and T cells to augment osteoclastogenesis. Taken together, S1P plays an important role in osteoclastogenesis regulation and in communication between osteoclasts and osteoblasts or T cells." . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . "eng" . . "IM" . . . . . . . . . . . . . . "MEDLINE" . "Dec" . "0261-4189" . . . . . . . "Print" . "13" . "25" . "NLM" . "Y" . "5840-51" . "2009-11-19" . . . . . . . . . . . . . . . . . . . . . . . . . . "2006" . "Sphingosine 1-phosphate as a regulator of osteoclast differentiation and osteoclast-osteoblast coupling." . "Department of Cell and Developmental Biology, BK21 Program, DRI, Seoul National University, 28 Yeongon-Dong, Chongno-Gu, Seoul 110-749, Korea." . "Journal Article" . "Research Support, Non-U.S. Gov't" .