title: TRPM7 Is Essential for RANKL-Induced Osteoclastogenesis.
abstract: The transient receptor potential melastatin type 7 (TRPM7) channel is a widely expressed non-selective cation channel with fusion to the C-terminal alpha kinase domain and regarded as a key regulator of whole body Mg(2+) homeostasis in mammals. However, the roles of TRPM7 during osteoclastogenesis in RAW264.7 cells and bone marrow-derived monocyte/macrophage precursor cells (BMMs) are not clear. In the present study, we investigate the roles of TRPM7 in osteoclastogenesis using methods of small interfering RNA (siRNA), RT-PCR, patch-clamp, and calcium imaging. RANKL (receptor activator of NF-κB ligand) stimulation did not affect the TRPM7 expression and TRPM7-mediated current was activated in HEK293, RAW264.7, and BMM cells by the regulation of Mg(2+). Knock-down of TRPM7 by siTRPM7 reduced intracellular Ca(2+) concentration ([Ca(2+)](i)) increases by 0 mM [Mg(2+)](e) in HEK293 cells and inhibited the generation of RANKL-induced Ca(2+) oscillations in RAW264.7 cells. Finally, knock-down of TRPM7 suppressed RANKL-mediated osteoclastogenesis such as activation and translocation of NFATc1, formation of multinucleated cells, and the bone resorptive activity, sequentially. These results suggest that TRPM7 plays an essential role in the RANKL-induced [Ca(2+)](i) oscillations that triggers the late stages of osteoclastogenesis.
authors: Department of Oral Biology, Yonsei University College of Dentistry, Seoul 120-752, Korea.
authors: Yu-Mi
authors: YM
authors: Yang
authors: Hwi-Hoon
authors: HH
authors: Jung
authors: Sung Jun
authors: SJ
authors: Lee
authors: Hyung-Jun
authors: HJ
authors: Choi
authors: Min Seuk
authors: MS
authors: Kim
authors: Dong Min
authors: DM
authors: Shin
keywords: Calcium signaling; Osteoclastogenesis; RANKL; TRPM7