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TRPM7 Is Essential for RANKL-Induced Osteoclastogenesis

Authors
 Yu-Mi Yang  ;  Hwi-Hoon Jung  ;  Sung Jun Lee  ;  Hyung-Jun Choi  ;  Min Seuk Kim  ;  Dong Min Shin 
Citation
 Korean Journal of Physiology & Pharmacology, Vol.17(1) : 65-71, 2013 
Journal Title
 Korean Journal of Physiology & Pharmacology 
ISSN
 1226-4512 
Issue Date
2013
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 Mg2+ 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 Mg2+. Knock-down of TRPM7 by siTRPM7 reduced intracellular Ca2+ concentration ([Ca2+]i) increases by 0 mM [Mg2+]e in HEK293 cells and inhibited the generation of RANKL-induced Ca2+ 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 [Ca2+]i oscillations that triggers the late stages of osteoclastogenesis.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/86370
DOI
10.4196/kjpp.2013.17.1.65
Appears in Collections:
1. Journal Papers (연구논문) > 2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실)
1. Journal Papers (연구논문) > 2. College of Dentistry (치과대학) > Dept. of Pediatric Dentistry (소아치과학교실)
1. Journal Papers (연구논문) > 5. Research Institutes (연구소) > Research Center for Human Natural Defense System (생체방어연구센터)
Yonsei Authors
신동민(Shin, Dong Min)
양유미(Yang, Yu Mi)
이성준(Lee, Sung Jun)
최형준(Choi, Hyung Jun)
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