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QKI deficiency leads to osteoporosis by promoting RANKL-induced osteoclastogenesis and disrupting bone metabolism

Quaking (QKI), an RNA-binding protein, has been reported to exhibit numerous biological functions, such as mRNA regulation, cancer suppression, and anti-inflammation. However, little known about the effects of QKI on bone metabolism. In this study, we used a monocyte/macrophage-specific QKI knockout...

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Autores principales: Du, Tianshu, Yan, Zhao, Zhu, Shu, Chen, Guo, Wang, Li, Ye, Zichen, Wang, Wenwen, Zhu, Qingsheng, Lu, Zifan, Cao, Xiaorui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7205892/
https://www.ncbi.nlm.nih.gov/pubmed/32382069
http://dx.doi.org/10.1038/s41419-020-2548-3
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author Du, Tianshu
Yan, Zhao
Zhu, Shu
Chen, Guo
Wang, Li
Ye, Zichen
Wang, Wenwen
Zhu, Qingsheng
Lu, Zifan
Cao, Xiaorui
author_facet Du, Tianshu
Yan, Zhao
Zhu, Shu
Chen, Guo
Wang, Li
Ye, Zichen
Wang, Wenwen
Zhu, Qingsheng
Lu, Zifan
Cao, Xiaorui
author_sort Du, Tianshu
collection PubMed
description Quaking (QKI), an RNA-binding protein, has been reported to exhibit numerous biological functions, such as mRNA regulation, cancer suppression, and anti-inflammation. However, little known about the effects of QKI on bone metabolism. In this study, we used a monocyte/macrophage-specific QKI knockout transgenic mouse model to investigate the effects of QKI deficiency on receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis. The loss of QKI promoted the formation of multinucleated tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts (OCs) from bone marrow macrophages, and upregulated the expression of OC-specific markers, including TRAP (Acp5) and cathepsin K (Ctsk). The pro-osteoclastogenesis effect of QKI deficiency was achieved by amplifying the signaling cascades of the NF-κB and mitogen-activated protein kinase (MAPK) pathways; then, signaling upregulated the activation of nuclear factor of activated T cells c1 (NFATc1), which is considered to be the core transcription factor that regulates OC differentiation. In addition, QKI deficiency could inhibit osteoblast (OB) formation through the inflammatory microenvironment. Taken together, our data suggest that QKI deficiency promoted OC differentiation and disrupted bone metabolic balance, and eventually led to osteopenia under physiological conditions and aggravated the degree of osteoporosis under pathological conditions.
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spelling pubmed-72058922020-05-13 QKI deficiency leads to osteoporosis by promoting RANKL-induced osteoclastogenesis and disrupting bone metabolism Du, Tianshu Yan, Zhao Zhu, Shu Chen, Guo Wang, Li Ye, Zichen Wang, Wenwen Zhu, Qingsheng Lu, Zifan Cao, Xiaorui Cell Death Dis Article Quaking (QKI), an RNA-binding protein, has been reported to exhibit numerous biological functions, such as mRNA regulation, cancer suppression, and anti-inflammation. However, little known about the effects of QKI on bone metabolism. In this study, we used a monocyte/macrophage-specific QKI knockout transgenic mouse model to investigate the effects of QKI deficiency on receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis. The loss of QKI promoted the formation of multinucleated tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts (OCs) from bone marrow macrophages, and upregulated the expression of OC-specific markers, including TRAP (Acp5) and cathepsin K (Ctsk). The pro-osteoclastogenesis effect of QKI deficiency was achieved by amplifying the signaling cascades of the NF-κB and mitogen-activated protein kinase (MAPK) pathways; then, signaling upregulated the activation of nuclear factor of activated T cells c1 (NFATc1), which is considered to be the core transcription factor that regulates OC differentiation. In addition, QKI deficiency could inhibit osteoblast (OB) formation through the inflammatory microenvironment. Taken together, our data suggest that QKI deficiency promoted OC differentiation and disrupted bone metabolic balance, and eventually led to osteopenia under physiological conditions and aggravated the degree of osteoporosis under pathological conditions. Nature Publishing Group UK 2020-05-07 /pmc/articles/PMC7205892/ /pubmed/32382069 http://dx.doi.org/10.1038/s41419-020-2548-3 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Du, Tianshu
Yan, Zhao
Zhu, Shu
Chen, Guo
Wang, Li
Ye, Zichen
Wang, Wenwen
Zhu, Qingsheng
Lu, Zifan
Cao, Xiaorui
QKI deficiency leads to osteoporosis by promoting RANKL-induced osteoclastogenesis and disrupting bone metabolism
title QKI deficiency leads to osteoporosis by promoting RANKL-induced osteoclastogenesis and disrupting bone metabolism
title_full QKI deficiency leads to osteoporosis by promoting RANKL-induced osteoclastogenesis and disrupting bone metabolism
title_fullStr QKI deficiency leads to osteoporosis by promoting RANKL-induced osteoclastogenesis and disrupting bone metabolism
title_full_unstemmed QKI deficiency leads to osteoporosis by promoting RANKL-induced osteoclastogenesis and disrupting bone metabolism
title_short QKI deficiency leads to osteoporosis by promoting RANKL-induced osteoclastogenesis and disrupting bone metabolism
title_sort qki deficiency leads to osteoporosis by promoting rankl-induced osteoclastogenesis and disrupting bone metabolism
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7205892/
https://www.ncbi.nlm.nih.gov/pubmed/32382069
http://dx.doi.org/10.1038/s41419-020-2548-3
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