Activation of G Proteins by Aluminum Fluoride Enhances RANKL-Mediated Osteoclastogenesis
The Korean Journal of Physiology and Pharmacology
;
: 427-433, 2013.
Article
in English
| WPRIM
| ID: wpr-727500
ABSTRACT
Receptor activator of NF-kappaB ligand (RANKL)-induced osteoclastogenesis is accompanied by intracellular Ca2+ mobilization in a form of oscillations, which plays essential roles by activating sequentially Ca2+/calmodulin-dependent protein kinase, calcineurin and NFATc1, necessary in the osteoclast differentiation. However, it is not known whether Ca2+ mobilization which is evoked in RANKL-independent way induces to differentiate into osteoclasts. In present study, we investigated Ca2+ mobilization induced by aluminum fluoride (AlF4-), a G-protein activator, with or without RANKL and the effects of AlF4- on the osteoclastogenesis in primary cultured mouse bone marrow-derived macrophages (BMMs). We show here that AlF4- induces intracellular Ca2+ concentration ([Ca2+]i) oscillations, which is dependent on extracellular Ca2+ influx. Notably, co-stimulation of AlF4- with RANKL resulted in enhanced NFATc1 expression and formation of tartrate-resistant acid phosphatase (TRAP) positive multinucleated cells. Additionally, we confirmed that mitogen-activated protein kinase (MAPK) is also activated by AlF4-. Taken together, these results demonstrate that G-protein would be a novel modulator responsible for [Ca2+]i oscillations and MAPK activation which lead to enhancement of RANKL-mediated osteoclastogenesis.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Osteoclasts
/
Protein Kinases
/
Acid Phosphatase
/
Aluminum Compounds
/
GTP-Binding Proteins
/
Calcineurin
/
Receptor Activator of Nuclear Factor-kappa B
/
Fluorides
/
Isoenzymes
/
Macrophages
Limits:
Animals
Language:
English
Journal:
The Korean Journal of Physiology and Pharmacology
Year:
2013
Type:
Article
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