Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 강상원 | * |
dc.date.accessioned | 2016-08-28T12:08:56Z | - |
dc.date.available | 2016-08-28T12:08:56Z | - |
dc.date.issued | 2010 | * |
dc.identifier.issn | 0021-9258 | * |
dc.identifier.other | OAK-6359 | * |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/220608 | - |
dc.description.abstract | RANKL (receptor activator of NF-κB ligand) induces osteoclastogenesis by activating multiple signaling pathways in osteoclast precursor cells, chief among which is induction of long lasting oscillations in the intracellular concentration of Ca2+ ([Ca2+]i). The [Ca 2+]i oscillations activate calcineurin, which activates the transcription factor NFATc1. The pathway by which RANKL induces [Ca 2+]i oscillations and osteoclastogenesis is poorly understood. Here we report the discovery of a novel pathway induced by RANKL to cause a long lasting increase in reactive oxygen species (ROS) and [Ca 2+]i oscillations that is essential for differentiation of bone marrow-derived monocytes into osteoclasts. The pathway includes RANKL-mediated stimulation of Rac1 to generate ROS, which stimulate phospholipase Cγ1 to evoke [Ca2+]i oscillations by stimulating Ca2+ release from the inositol 1,4,5-trisphosphate pool and STIM1-regulated Ca2+ influx. Induction and activation of the pathway is observed only after 24-h stimulation with RANKL and lasts for at least 3 days. The physiological role of the pathway is demonstrated in mice with deletion of the Peroxiredoxin II gene and results in a mark increase is ROS and, consequently, a decrease in bone density. Moreover, bone marrow-derived monocytes in PrxII-/- primary culture show increased ROS and spontaneous [Ca2+]i oscillations. These findings identify the primary RANKL-stimulated pathway to trigger the late stages of osteoclastogenesis and regulate bone resorption. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc. | * |
dc.language | English | * |
dc.title | RANKL-mediated reactive oxygen species pathway that induces long lasting Ca2+ oscillations essential for osteoclastogenesis | * |
dc.type | Article | * |
dc.relation.issue | 10 | * |
dc.relation.volume | 285 | * |
dc.relation.index | SCI | * |
dc.relation.index | SCIE | * |
dc.relation.index | SCOPUS | * |
dc.relation.startpage | 6913 | * |
dc.relation.lastpage | 6921 | * |
dc.relation.journaltitle | Journal of Biological Chemistry | * |
dc.identifier.doi | 10.1074/jbc.M109.051557 | * |
dc.identifier.wosid | WOS:000275415600005 | * |
dc.identifier.scopusid | 2-s2.0-77951213242 | * |
dc.author.google | Kim M.S. | * |
dc.author.google | Yang Y.-M. | * |
dc.author.google | Son A. | * |
dc.author.google | Tian Y.S. | * |
dc.author.google | Lee S.-I. | * |
dc.author.google | Kang S.W. | * |
dc.author.google | Muallem S. | * |
dc.author.google | Shin D.M. | * |
dc.contributor.scopusid | 강상원(55731433900) | * |
dc.date.modifydate | 20240118155300 | * |