L-type Ca2+ channel agonist inhibits RANKL-induced osteoclast formation via NFATc1 down-regulation
DC Field | Value | Language |
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dc.contributor.author | Noh, A. Long Sae Mi | - |
dc.contributor.author | Park, Hyojung | - |
dc.contributor.author | Zheng, Ting | - |
dc.contributor.author | Ha, Hyun-Il | - |
dc.contributor.author | Yim, Mijung | - |
dc.date.available | 2021-02-22T13:16:44Z | - |
dc.date.issued | 2011-08-01 | - |
dc.identifier.issn | 0024-3205 | - |
dc.identifier.issn | 1879-0631 | - |
dc.identifier.uri | https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/12520 | - |
dc.description.abstract | Aims: BayK 8644 is an L-type Ca2+ channel agonist that enhances Ca2+ influx and elevates cytosolic Ca2+. As intracellular calcium plays a key role in osteoclast formation, we investigated the effects of BayK 8644 in cultures of bone marrow-derived precursor cells with macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappaB ligand (RANKL). Main methods: We performed an osteoclast formation assay, a pit formation assay, real-time PCR, and Western blot analysis. Key findings: BayK 8644 concentration-dependently suppressed osteoclastogenesis, as well as the expression of osteoclastic marker genes. It also decreased osteoclastic bone resorption on a dentine slice. While the RANKL-stimulated induction of IL-1 beta and IL-6 was not affected, TNF-alpha induction was reduced by BayK 8644 treatment. In addition, BayK 8644 blocked la degradation and the induction of nuclear factor of activated T cells c1 (NFATc1), the master regulator of osteoclast differentiation, following RANKL stimulation. Finally, forced expression of NFATc1 reversed the inhibitory effect of BayK 8644 on osteoclastogenesis, suggesting that NFATc1 is a downstream target for the anti-osteoclastogenic action of BayK 8644. Taken together, our data suggest that BayK 8644 has an anti-osteoclastogenic effect by inhibiting RANKL-induced activation of NF-kappa B pathways, thereby suppressing the gene expression of NFATc1 in osteoclast precursors. Significance: Our results provide a molecular understanding of the inhibitory effect of the L-type Ca2+ channel agonist, BayK 8644, on osteoclastogenesis. (C) 2011 Elsevier Inc. All rights reserved. | - |
dc.format.extent | 6 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | PERGAMON-ELSEVIER SCIENCE LTD | - |
dc.title | L-type Ca2+ channel agonist inhibits RANKL-induced osteoclast formation via NFATc1 down-regulation | - |
dc.type | Article | - |
dc.publisher.location | 영국 | - |
dc.identifier.doi | 10.1016/j.lfs.2011.05.009 | - |
dc.identifier.scopusid | 2-s2.0-80051795594 | - |
dc.identifier.wosid | 000293114300003 | - |
dc.identifier.bibliographicCitation | LIFE SCIENCES, v.89, no.5-6, pp 159 - 164 | - |
dc.citation.title | LIFE SCIENCES | - |
dc.citation.volume | 89 | - |
dc.citation.number | 5-6 | - |
dc.citation.startPage | 159 | - |
dc.citation.endPage | 164 | - |
dc.type.docType | Article | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | sci | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Research & Experimental Medicine | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Medicine, Research & Experimental | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.subject.keywordPlus | FORMATION IN-VITRO | - |
dc.subject.keywordPlus | DC-STAMP | - |
dc.subject.keywordPlus | SIGNALING PATHWAYS | - |
dc.subject.keywordPlus | BONE-RESORPTION | - |
dc.subject.keywordPlus | DIFFERENTIATION | - |
dc.subject.keywordPlus | CALCIUM | - |
dc.subject.keywordPlus | RECEPTOR | - |
dc.subject.keywordPlus | CELLS | - |
dc.subject.keywordPlus | FUSION | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordAuthor | L-type Ca2+ channel | - |
dc.subject.keywordAuthor | BayK 8644 | - |
dc.subject.keywordAuthor | Osteoclast | - |
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