Effects of Inositol 1,4,5-triphosphate on Osteoclast Differentiation in RANKL-induced Osteoclastogenesis

• 영문명: Effects of Inositol 1,4,5-triphosphate on Osteoclast Differentiation in RANKL-induced Osteoclastogenesis
• 발행기관: 대한생리학회-대한약리학회
• 저자명: Aran Son Min Seuk Kim Hae Jo Hae Mi Byun Dong Min Shin
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제16권 제1호, 31~36쪽, 전체 6쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2012.01.01

영문 초록

The receptor activator of NF-ՊB ligand (RANKL) signal is an activator of tumor necrosis factor receptor-associated factor 6 (TRAF6), which leads to the activation of NF-ՊB and other signal transduction pathways essential for osteoclastogenesis, such as Ca^2＋ signaling. However, the intra</SUP>cellular 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 Ca^2＋ signaling proteins such as IP₃ receptors (IP₃Rs), 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 IP₃ was observed in RAW264.7 cells transfected with green fluorescent protein (GFP)-tagged pleckstrin homology (PH) domains of phospholipase C (PLC) Մ, 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.

키워드

Inositol 1,4,5-trisphosphate RANKL Osteoclastogenesis Ca^2＋ signaling