دورية أكاديمية
Zinc inhibits osteoclast differentiation by suppression of Ca2+-Calcineurin-NFATc1 signaling pathway
| العنوان: | Zinc inhibits osteoclast differentiation by suppression of Ca2+-Calcineurin-NFATc1 signaling pathway |
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| المساهمون: | Kwang Hwan Park, Boryung Park, Dong Suk Yoon, Seung-Hyun Kwon, Dong Min Shin, Jin Woo Lee, Hyun Gyu Lee, Jae-Hyuck Shim, Jeon Han Park, Jae Myun Lee, Lee, Jin Woo, Lee, Hyun Gyu, Park, Kwang Hwan, Park, Bo Ryung, Park, Jeon Han, Shin, Dong Min, Lee, Jae Myun |
| المصدر: | T201303398.pdf |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Animals, Bone Marrow Cells/cytology, Calcineurin/metabolism, Calcium/metabolism, Cell Differentiation/drug effects, Cell Line, Cells, Cultured, Mice, Monocytes/drug effects, Monocytes/metabolism, NFATC Transcription Factors/genetics, NFATC Transcription Factors/metabolism, Osteoclasts/cytology, Osteoclasts/drug effects, RANK Ligand/metabolism, Signal Transduction/drug effects, Zinc/pharmacology, Zinc, Bone loss, Osteoclast, NFATc1, Calcineurin, Ca2+ oscillation |
| الوصف: | BACKGROUND: 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-觀B 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-觀B 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 C款1 (p-PLC款1), 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. ; open |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| تدمد: | 1478-811X |
| العلاقة: | CELL COMMUNICATION AND SIGNALING; J00480; OAK-2013-01929; https://ir.ymlib.yonsei.ac.kr/handle/22282913/88046Test; T201303398; CELL COMMUNICATION AND SIGNALING, Vol.11(1) : 74, 2013 |
| DOI: | 10.1186/1478-811X-11-74 |
| الإتاحة: | https://doi.org/10.1186/1478-811X-11-74Test https://ir.ymlib.yonsei.ac.kr/handle/22282913/88046Test |
| حقوق: | CC BY-NC-ND 2.0 KR ; https://creativecommons.org/licenses/by-nc-nd/2.0/krTest/ ; free |
| رقم الانضمام: | edsbas.BD421B64 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 1478811X |
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| DOI: | 10.1186/1478-811X-11-74 |