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Effects of Inositol 1,4,5-triphosphate on Osteoclast Differentiation in RANKL-induced Osteoclastogenesis
The Korean Journal of Physiology and Pharmacology ; : 31-36, 2012.
Article in English | WPRIM | ID: wpr-727561
ABSTRACT
The receptor activator of NF-kappaB ligand (RANKL) signal is an activator of tumor necrosis factor receptor-associated factor 6 (TRAF6), which leads to the activation of NF-kappaB and other signal transduction pathways essential for osteoclastogenesis, such as Ca2+ signaling. However, the intracellular levels of inositol 1,4,5-trisphosphate (IP3) and IP3-mediated cellular function of RANKL during osteoclastogenesis are not known. In the present study, we determined the levels of IP3 and evaluated IP3-mediated osteoclast differentiation and osteoclast activity by RANKL treatment of mouse leukemic macrophage cells (RAW 264.7) and mouse bone marrow-derived monocyte/macrophage precursor cells (BMMs). During osteoclastogenesis, the expression levels of Ca2+ signaling proteins such as IP3 receptors (IP3Rs), plasma membrane Ca2+ ATPase, and sarco/endoplasmic reticulum Ca2+ ATPase type2 did not change by RANKL treatment for up to 6 days in both cell types. At 24 h after RANKL treatment, a higher steady-state level of IP3 was observed in RAW264.7 cells transfected with green fluorescent protein (GFP)-tagged pleckstrin homology (PH) domains of phospholipase C (PLC) delta, a probe specifically detecting intracellular IP3 levels. In BMMs, the inhibition of PLC with U73122 [a specific inhibitor of phospholipase C (PLC)] and of IP3Rs with 2-aminoethoxydiphenyl borate (2APB; a non-specific inhibitor of IP3Rs) inhibited the generation of RANKL-induced multinucleated cells and decreased the bone-resorption rate in dentin slice, respectively. These results suggest that intracellular IP3 levels and the IP3-mediated signaling pathway play an important role in RANKL-induced osteoclastogenesis.
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Full text: Available Index: WPRIM (Western Pacific) Main subject: Osteoclasts / Type C Phospholipases / Phosphoproteins / Pyrrolidinones / Reticulum / Boron Compounds / Blood Proteins / Signal Transduction / Proteins / Inositol 1,4,5-Trisphosphate Limits: Animals Language: English Journal: The Korean Journal of Physiology and Pharmacology Year: 2012 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Osteoclasts / Type C Phospholipases / Phosphoproteins / Pyrrolidinones / Reticulum / Boron Compounds / Blood Proteins / Signal Transduction / Proteins / Inositol 1,4,5-Trisphosphate Limits: Animals Language: English Journal: The Korean Journal of Physiology and Pharmacology Year: 2012 Type: Article