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Bumetanide, the specific inhibitor of Na+-K+-2C1- cotransport, inhibits 1α,25-dihydroxyvitamin D3-induced osteoclastogenesis in a mouse co-culture system

Authors
 Hyun-A Lee  ;  Hyunjoo Jeong  ;  Syng-Ill Lee  ;  Seung-Ho Ohk  ;  Dong Min Shin  ;  Jeong-Taeg Seo  ;  Yun-Jung Yoo  ;  Mi Young Nam  ;  Eun-Young Kim 
Citation
 EXPERIMENTAL PHYSIOLOGY, Vol.88(5) : 569-574, 2003 
Journal Title
 EXPERIMENTAL PHYSIOLOGY 
ISSN
 0958-0670 
Issue Date
2003
Abstract
The Na(+)-K(+)-2Cl(-) cotransporter (NKCC1) is responsible for ion transport across the secretory and absorptive epithelia, the regulation of cell volume, and possibly the modulation of cell growth and development. It has been reported that a variety of cells, including osteoblasts, contain this cotransporter. In this study, the physiological role of NKCC1 in osteoclastogenesis was exploited in a co-culture system. Bumetanide, a specific inhibitor of NKCC1, reduced the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells. In order to investigate the mechanism by which bumetanide inhibits osteoclastogenesis, the mRNA expressions of the receptor activator of nuclear factor (NF)-kappaB ligand (RANKL) and osteoprotegerin (OPG) were analysed by RT-PCR. Exposure of osteoblastic cells to a medium containing 1 micro M bumetanide reduced RANKL mRNA expression induced by 10 nM 1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3, in a dose-dependent manner. In addition, RANKL expression was also analysed with enzyme-linked immunosorbant assay (ELISA) using anti-RANKL antibody. The expression of RANKL was decreased with the increase of bumetanide concentration. In contrast, the expression of OPG mRNA, a novel tumour necrosis factor (TNF) receptor family member was increased in the presence of bumetanide. These results imply that bumetanide inhibits osteoclast differentiation by reducing the RANKL/OPG ratio in osteoblastic cells. However, no significant difference in M-CSF mRNA expression was observed when bumetanide was added. Also, we found that the phosphorylation of c-Jun NH2-terminal kinase (JNK), which regulates the activity of various transcriptional factors, was reduced by bumetanide treatment. Conclusively, these findings suggest that NKCC1 in osteoblasts has a pivotal role in 1alpha,25(OH)2D3-induced osteoclastogenesis partly via the phosphorylation of JNK.
Files in This Item:
T200306781.pdf Download
DOI
OAK-2003-01300
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Seo, Jeong Taeg(서정택) ORCID logo https://orcid.org/0000-0003-2697-0251
Shin, Dong Min(신동민) ORCID logo https://orcid.org/0000-0001-6042-0435
Yoo, Yun Jung(유윤정) ORCID logo https://orcid.org/0000-0002-0045-9597
Lee, Syng Ill(이승일)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/114460
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