Document Detail

Nitric oxide enhances osteoclastogenesis possibly by mediating cell fusion.
MedLine Citation:
PMID:  19389479     Owner:  NLM     Status:  MEDLINE    
Osteoclasts are multinucleated bone resorbing cells which form by fusion of pre-osteoclasts. Here, we investigate how nitric oxide (NO) affects osteoclastogenesis. Time lapse photomicrography, using the fluorescent NO indicator dye, 4,5-diaminofluorescein diacetate, revealed an intense NO signal in pre-osteoclasts preceding cell fusion. Osteoclastogenesis in RAW264.7 cells increased when exposed to the NO synthase inhibitor, L-NMMA (0.25 microM), for the initial 48 h. In contrast, pre-osteoclast fusion decreased when RAW264.7 cells were exposed to L-NMMA from 48 to 96 h. Both NO synthase inhibitors, L-NMMA and L-NAME, decreased osteoclast formation during this time period. The inhibitory effect of L-NMMA on osteoclast formation was abolished with increasing concentrations (25-200 ng/ml) of sRANKL suggesting signaling cross talk. NO donors increased osteoclast formation in a dose-dependent manner, with greatest stimulation at 15 microM NOC-12 (2.3 fold) and 5 microM NOC-18 (2.4 fold). Measuring nitrite (NO end product) daily from culture media of RAW264.7 cells undergoing osteoclastogenesis revealed that an increase in NO production coincided with the fusion of pre-osteoclasts (day 4). Inhibiting fusion by plating cells on polystyrene dishes pre-coated with poly-(L-lysine) decreased both osteoclast formation and NO production. To address if NO mediates fusion through the actin cytoskeleton, actin free barbed ends were measured. 0.25 microM L-NMMA decreased, while 15 microM NOC-12 and 5 microM NOC-18 increased actin free barbed ends. We hypothesize that while NO initially negatively regulates pre-osteoclast differentiation; it later facilitates the fusion of mononuclear pre-osteoclasts, possibly by up regulating actin remodeling.
Dorrin Nilforoushan; Azza Gramoun; Michael Glogauer; Morris F Manolson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-04-21
Journal Detail:
Title:  Nitric oxide : biology and chemistry / official journal of the Nitric Oxide Society     Volume:  21     ISSN:  1089-8611     ISO Abbreviation:  Nitric Oxide     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-07-14     Completed Date:  2009-10-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9709307     Medline TA:  Nitric Oxide     Country:  United States    
Other Details:
Languages:  eng     Pagination:  27-36     Citation Subset:  IM    
Faculty of Dentistry, University of Toronto, Toronto, ON, Canada.
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MeSH Terms
Acid Phosphatase / metabolism
Actins / metabolism
Analysis of Variance
Cell Differentiation / drug effects
Cell Fusion
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Survival / drug effects
Cells, Cultured
Enzyme Inhibitors / pharmacology
Isoenzymes / metabolism
Nitric Oxide / biosynthesis,  metabolism*
Nitric Oxide Donors / pharmacology
Nitric Oxide Synthase / antagonists & inhibitors,  metabolism
Nitrites / metabolism
Nitroso Compounds / pharmacology
Osteoclasts / cytology*,  drug effects,  metabolism*
Polylysine / pharmacology
omega-N-Methylarginine / pharmacology
Reg. No./Substance:
0/Actins; 0/Enzyme Inhibitors; 0/Isoenzymes; 0/NOC 18; 0/Nitric Oxide Donors; 0/Nitrites; 0/Nitroso Compounds; 10102-43-9/Nitric Oxide; 17035-90-4/omega-N-Methylarginine; 25104-18-1/Polylysine; EC Oxide Synthase; EC 3.1.3.-/tartrate-resistant acid phosphatase; EC Phosphatase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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