Effects of inositol 1,4,5-triphosphate on osteoclast differentiation in RANKL-induced osteoclastogenesis

Aran Son, Min Seuk Kim, Hae Jo, Hae Mi Byun, Dong Min Shin

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


The receptor activator of NF-κB ligand (RANKL) signal is an activator of tumor necrosis factor receptor-associated factor 6 (TRAF6), which leads to the activation of NF-κB and other signal transduction pathways essential for osteoclastogenesis, such as Ca 2+ signaling. However, the intra-cellular levels of inositol 1,4,5-trisphosphate (IP 3) and IP 3-mediated cellular function of RANKL during osteoclastogenesis are not known. In the present study, we determined the levels of IP 3 and evaluated IP 3-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 Ca 2+ signaling proteins such as IP 3 receptors (IP 3RS), plasma membrane Ca 2+ ATPase, and sarco/endoplasmic reticulum Ca 2+ 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 IP 3 was observed in RAW264.7 cells transfected with green fluorescent protein (GFP)-tagged pleckstrin homology (PH) domains of phospholipase C (PLC) δ, a probe specifically detecting intracellular IP 3 levels. In BMMs, the inhibition of PLC with U73122 [a specific inhibitor of phospholipase C (PLC)] and of IP 3RS with 2-aminoethoxydiphenyl borate (2APB; a non-specific inhibitor of IP 3Rs) inhibited the generation of RANKL-induced multinucleated cells and decreased the bone-resorption rate in dentin slice, respectively. These results suggest that intracellular IP 3 levels and the IP 3-mediated signaling pathway play an important role in RANKL-induced osteoclastogenesis.

Original languageEnglish
Pages (from-to)31-36
Number of pages6
JournalKorean Journal of Physiology and Pharmacology
Issue number1
Publication statusPublished - 2012 Feb

All Science Journal Classification (ASJC) codes

  • Physiology
  • Pharmacology


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