title: Dynamic visualization of RANKL and Th17-mediated osteoclast function.
abstract: Osteoclasts are bone resorbing, multinucleate cells that differentiate from mononuclear macrophage/monocyte-lineage hematopoietic precursor cells. Although previous studies have revealed important molecular signals, how the bone resorptive functions of such cells are controlled in vivo remains less well characterized. Here, we visualized fluorescently labeled mature osteoclasts in intact mouse bone tissues using intravital multiphoton microscopy. Within this mature population, we observed cells with distinct motility behaviors and function, with the relative proportion of static - bone resorptive (R) to moving - nonresorptive (N) varying in accordance with the pathophysiological conditions of the bone. We also found that rapid application of the osteoclast-activation factor RANKL converted many N osteoclasts to R, suggesting a novel point of action in RANKL-mediated control of mature osteoclast function. Furthermore, we showed that Th17 cells, a subset of RANKL-expressing CD4+ T cells, could induce rapid N-to-R conversion of mature osteoclasts via cell-cell contact. These findings provide new insights into the activities of mature osteoclasts in situ and identify actions of RANKL-expressing Th17 cells in inflammatory bone destruction.
authors: Laboratory of Cellular Dynamics, WPI–Immunology Frontier Research Center, Osaka University, Osaka, Japan.
authors: Junichi
authors: J
authors: Kikuta
authors: Yoh
authors: Y
authors: Wada
authors: Toshiyuki
authors: T
authors: Kowada
authors: Ze
authors: Z
authors: Wang
authors: Ge-Hong
authors: GH
authors: Sun-Wada
authors: Issei
authors: I
authors: Nishiyama
authors: Shin
authors: S
authors: Mizukami
authors: Nobuhiko
authors: N
authors: Maiya
authors: Hisataka
authors: H
authors: Yasuda
authors: Atsushi
authors: A
authors: Kumanogoh
authors: Kazuya
authors: K
authors: Kikuchi
authors: Ronald N
authors: RN
authors: Germain
authors: Masaru
authors: M
authors: Ishii
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D036641:Microscopy, Fluorescence, Multiphoton; D010010:Osteoclasts / Q000187:drug effects / Q000502:physiology*; D053245:RANK Ligand / Q000008:administration & dosage / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics; D058504:Th17 Cells / Q000502:physiology*; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism
chemical_list: C484226:Atp6ap1 protein, mouse; D053245:RANK Ligand; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C505689:Tnfsf11 protein, mouse; D025262:Vacuolar Proton-Translocating ATPases