Activation of G Proteins by Aluminum Fluoride Enhances RANKLMediated Osteoclastogenesis

다국어 초록 (Multilingual Abstract)

Receptor activator of NF-κB 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.

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