Dynamic network biomarker identifies cdkn1a-mediated bone mineralization in the triggering phase of osteoporosis

The identification of predictive markers to determine the triggering phase prior to the onset of osteoporosis is essential to mitigate further irrevocable deterioration. To determine the early warning signs before osteoporosis, we used the dynamic network biomarker (DNB) approach to analyze time-ser...

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Autores principales: Guo, Weiming, Jin, Peng, Li, Ruomei, Huang, Lu, Liu, Zhen, Li, Hairui, Zhou, Ting, Fang, Bing, Xia, Lunguo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9898265/
https://www.ncbi.nlm.nih.gov/pubmed/36599933
http://dx.doi.org/10.1038/s12276-022-00915-9
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author Guo, Weiming
Jin, Peng
Li, Ruomei
Huang, Lu
Liu, Zhen
Li, Hairui
Zhou, Ting
Fang, Bing
Xia, Lunguo
author_facet Guo, Weiming
Jin, Peng
Li, Ruomei
Huang, Lu
Liu, Zhen
Li, Hairui
Zhou, Ting
Fang, Bing
Xia, Lunguo
author_sort Guo, Weiming
collection PubMed
description The identification of predictive markers to determine the triggering phase prior to the onset of osteoporosis is essential to mitigate further irrevocable deterioration. To determine the early warning signs before osteoporosis, we used the dynamic network biomarker (DNB) approach to analyze time-series gene expression data in a zebrafish osteoporosis model, which revealed that cyclin-dependent kinase inhibitor 1 A (cdkn1a) is a core DNB. We found that cdkn1a negatively regulates osteogenesis, as evidenced by loss-of-function and gain-of-function studies. Specifically, CRISPR/Cas9-mediated cdkn1a knockout in zebrafish significantly altered skeletal development and increased bone mineralization, whereas inducible cdkn1a expression significantly contributed to osteoclast differentiation. We also found several mechanistic clues that cdkn1a participates in osteoclast differentiation by regulating its upstream signaling cascades. To summarize, in this study, we provided new insights into the dynamic nature of osteoporosis and identified cdkn1a as an early-warning signal of osteoporosis onset.
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spelling pubmed-98982652023-02-16 Dynamic network biomarker identifies cdkn1a-mediated bone mineralization in the triggering phase of osteoporosis Guo, Weiming Jin, Peng Li, Ruomei Huang, Lu Liu, Zhen Li, Hairui Zhou, Ting Fang, Bing Xia, Lunguo Exp Mol Med Article The identification of predictive markers to determine the triggering phase prior to the onset of osteoporosis is essential to mitigate further irrevocable deterioration. To determine the early warning signs before osteoporosis, we used the dynamic network biomarker (DNB) approach to analyze time-series gene expression data in a zebrafish osteoporosis model, which revealed that cyclin-dependent kinase inhibitor 1 A (cdkn1a) is a core DNB. We found that cdkn1a negatively regulates osteogenesis, as evidenced by loss-of-function and gain-of-function studies. Specifically, CRISPR/Cas9-mediated cdkn1a knockout in zebrafish significantly altered skeletal development and increased bone mineralization, whereas inducible cdkn1a expression significantly contributed to osteoclast differentiation. We also found several mechanistic clues that cdkn1a participates in osteoclast differentiation by regulating its upstream signaling cascades. To summarize, in this study, we provided new insights into the dynamic nature of osteoporosis and identified cdkn1a as an early-warning signal of osteoporosis onset. Nature Publishing Group UK 2023-01-04 /pmc/articles/PMC9898265/ /pubmed/36599933 http://dx.doi.org/10.1038/s12276-022-00915-9 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Guo, Weiming
Jin, Peng
Li, Ruomei
Huang, Lu
Liu, Zhen
Li, Hairui
Zhou, Ting
Fang, Bing
Xia, Lunguo
Dynamic network biomarker identifies cdkn1a-mediated bone mineralization in the triggering phase of osteoporosis
title Dynamic network biomarker identifies cdkn1a-mediated bone mineralization in the triggering phase of osteoporosis
title_full Dynamic network biomarker identifies cdkn1a-mediated bone mineralization in the triggering phase of osteoporosis
title_fullStr Dynamic network biomarker identifies cdkn1a-mediated bone mineralization in the triggering phase of osteoporosis
title_full_unstemmed Dynamic network biomarker identifies cdkn1a-mediated bone mineralization in the triggering phase of osteoporosis
title_short Dynamic network biomarker identifies cdkn1a-mediated bone mineralization in the triggering phase of osteoporosis
title_sort dynamic network biomarker identifies cdkn1a-mediated bone mineralization in the triggering phase of osteoporosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9898265/
https://www.ncbi.nlm.nih.gov/pubmed/36599933
http://dx.doi.org/10.1038/s12276-022-00915-9
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