Document Detail

Dynamic visualization of RANKL and Th17-mediated osteoclast function.
MedLine Citation:
PMID:  23321670     Owner:  NLM     Status:  MEDLINE    
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.
Junichi Kikuta; Yoh Wada; Toshiyuki Kowada; Ze Wang; Ge-Hong Sun-Wada; Issei Nishiyama; Shin Mizukami; Nobuhiko Maiya; Hisataka Yasuda; Atsushi Kumanogoh; Kazuya Kikuchi; Ronald N Germain; Masaru Ishii
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-01-16
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  123     ISSN:  1558-8238     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-04-19     Completed Date:  2013-05-13     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  866-73     Citation Subset:  AIM; IM    
Laboratory of Cellular Dynamics, WPI–Immunology Frontier Research Center, Osaka University, Osaka, Japan.
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MeSH Terms
Bone Resorption / etiology,  pathology,  physiopathology
Cell Communication / physiology
Cell Differentiation / drug effects,  physiology
Mice, Transgenic
Microscopy, Fluorescence, Multiphoton
Osteoclasts / drug effects,  physiology*
RANK Ligand / administration & dosage,  genetics,  physiology*
Recombinant Fusion Proteins / genetics,  metabolism
Recombinant Proteins / administration & dosage,  genetics
Th17 Cells / physiology*
Vacuolar Proton-Translocating ATPases / genetics,  metabolism
Reg. No./Substance:
0/Atp6ap1 protein, mouse; 0/RANK Ligand; 0/Recombinant Fusion Proteins; 0/Recombinant Proteins; 0/Tnfsf11 protein, mouse; EC 3.6.1.-/Vacuolar Proton-Translocating ATPases

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