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Zinc inhibits osteoclast differentiation by suppression of Ca2+-Calcineurin-NFATc1 signaling pathway

DC FieldValueLanguage
dc.contributor.author이진우-
dc.contributor.author이현규-
dc.contributor.author박광환-
dc.contributor.author박보령-
dc.contributor.author박전한-
dc.contributor.author신동민-
dc.contributor.author이재면-
dc.date.accessioned2014-12-18T09:22:16Z-
dc.date.available2014-12-18T09:22:16Z-
dc.date.issued2013-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/88046-
dc.description.abstractBACKGROUND: Zinc, an essential trace element, inhibits osteoclast differentiation in vitro and in vivo. The molecular mechanism for the inhibitory effect of zinc, however, is poorly understood. The purpose of this study was to investigate the effect of zinc and determine its molecular mechanism on receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis in mouse bone marrow-derived monocyte cells (BMMs) and RAW264.7 cells. RESULTS: In BMMs, zinc treatment during osteoclast differentiation decreased RANKL-induced osteoclast formation in a dose-dependent manner. We show that zinc suppressed the mRNA levels of nuclear factor of activated T-cells, cytoplasmic 1 (Nfatc1). Zinc also accumulated phospho-Nfatc1 (p-Nfatc1) in the cytosol in a dose-dependent manner and inhibited the translocation of Nfatc1 to the nucleus in RAW264.7 cells. Zinc suppressed the activities of Nfatc1 in the nucleus without changing the activities of NF-κB in RAW264.7 cells. In contrast, calcineurin activity decreased in response to zinc but its protein level was unchanged. RANKL-induced Ca2+ oscillations were inhibited by zinc treatment, but phospho-phospholipase Cγ1 (p-PLCγ1), the upstream signaling molecule of Ca2+ oscillations, was unaffected. Moreover, a constitutively active form of Nfatc1 obviously rescued suppression of osteoclastogenesis by zinc. CONCLUSIONS: Taken together, these results demonstrate for the first time that the inhibitory effect of zinc during osteoclastogesis is caused by suppressing the Ca2+-Calcineurin-NFATc1 signaling pathway. Thus, zinc may be a useful therapeutic candidate for the prevention of bone loss caused by NFATc1 activation in osteoclasts.-
dc.description.statementOfResponsibilityopen-
dc.relation.isPartOfCELL COMMUNICATION AND SIGNALING-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAnimals-
dc.subject.MESHBone Marrow Cells/cytology-
dc.subject.MESHCalcineurin/metabolism*-
dc.subject.MESHCalcium/metabolism-
dc.subject.MESHCell Differentiation/drug effects-
dc.subject.MESHCell Line-
dc.subject.MESHCells, Cultured-
dc.subject.MESHMice-
dc.subject.MESHMonocytes/drug effects*-
dc.subject.MESHMonocytes/metabolism-
dc.subject.MESHNFATC Transcription Factors/genetics-
dc.subject.MESHNFATC Transcription Factors/metabolism*-
dc.subject.MESHOsteoclasts/cytology-
dc.subject.MESHOsteoclasts/drug effects*-
dc.subject.MESHRANK Ligand/metabolism-
dc.subject.MESHSignal Transduction/drug effects-
dc.subject.MESHZinc/pharmacology*-
dc.titleZinc inhibits osteoclast differentiation by suppression of Ca2+-Calcineurin-NFATc1 signaling pathway-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Orthopedic Surgery (정형외과학)-
dc.contributor.googleauthorKwang Hwan Park-
dc.contributor.googleauthorBoryung Park-
dc.contributor.googleauthorDong Suk Yoon-
dc.contributor.googleauthorSeung-Hyun Kwon-
dc.contributor.googleauthorDong Min Shin-
dc.contributor.googleauthorJin Woo Lee-
dc.contributor.googleauthorHyun Gyu Lee-
dc.contributor.googleauthorJae-Hyuck Shim-
dc.contributor.googleauthorJeon Han Park-
dc.contributor.googleauthorJae Myun Lee-
dc.identifier.doi10.1186/1478-811X-11-74-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA03230-
dc.contributor.localIdA03289-
dc.contributor.localIdA01481-
dc.contributor.localIdA01641-
dc.contributor.localIdA02091-
dc.contributor.localIdA03071-
dc.contributor.localIdA01437-
dc.relation.journalcodeJ00480-
dc.identifier.eissn1478-811X-
dc.identifier.pmid24088289-
dc.subject.keywordZinc-
dc.subject.keywordBone loss-
dc.subject.keywordOsteoclast-
dc.subject.keywordNFATc1-
dc.subject.keywordCalcineurin-
dc.subject.keywordCa2+ oscillation-
dc.contributor.alternativeNameLee, Jin Woo-
dc.contributor.alternativeNameLee, Hyun Gyu-
dc.contributor.alternativeNamePark, Kwang Hwan-
dc.contributor.alternativeNamePark, Bo Ryung-
dc.contributor.alternativeNamePark, Jeon Han-
dc.contributor.alternativeNameShin, Dong Min-
dc.contributor.alternativeNameLee, Jae Myun-
dc.contributor.affiliatedAuthorLee, Jin Woo-
dc.contributor.affiliatedAuthorLee, Hyun Gyu-
dc.contributor.affiliatedAuthorPark, Bo Ryung-
dc.contributor.affiliatedAuthorPark, Jeon Han-
dc.contributor.affiliatedAuthorShin, Dong Min-
dc.contributor.affiliatedAuthorLee, Jae Myun-
dc.contributor.affiliatedAuthorPark, Kwang Hwan-
dc.rights.accessRightsfree-
dc.citation.volume11-
dc.citation.number1-
dc.citation.startPage74-
dc.identifier.bibliographicCitationCELL COMMUNICATION AND SIGNALING, Vol.11(1) : 74, 2013-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Orthopedic Surgery (정형외과학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers

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