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Fibulin2: a negative regulator of BMSC osteogenic differentiation in infected bone fracture healing

Bone fracture remains a common occurrence, with a population-weighted incidence of approximately 3.21 per 1000. In addition, approximately 2% to 50% of patients with skeletal fractures will develop an infection, one of the causes of disordered bone healing. Dysfunction of bone marrow mesenchymal ste...

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Autores principales: Li, Shi-Dan, Xing, Wei, Wang, Shao-Chuan, Li, You-Bin, Jiang, Hao, Zheng, Han-Xuan, Li, Xiao-Ming, Yang, Jing, Guo, De-Bin, Xie, Xiao-Yu, Jiang, Ren-Qing, Fan, Chao, Li, Lei, Xu, Xiang, Fei, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9981700/
https://www.ncbi.nlm.nih.gov/pubmed/36797542
http://dx.doi.org/10.1038/s12276-023-00942-0
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author Li, Shi-Dan
Xing, Wei
Wang, Shao-Chuan
Li, You-Bin
Jiang, Hao
Zheng, Han-Xuan
Li, Xiao-Ming
Yang, Jing
Guo, De-Bin
Xie, Xiao-Yu
Jiang, Ren-Qing
Fan, Chao
Li, Lei
Xu, Xiang
Fei, Jun
author_facet Li, Shi-Dan
Xing, Wei
Wang, Shao-Chuan
Li, You-Bin
Jiang, Hao
Zheng, Han-Xuan
Li, Xiao-Ming
Yang, Jing
Guo, De-Bin
Xie, Xiao-Yu
Jiang, Ren-Qing
Fan, Chao
Li, Lei
Xu, Xiang
Fei, Jun
author_sort Li, Shi-Dan
collection PubMed
description Bone fracture remains a common occurrence, with a population-weighted incidence of approximately 3.21 per 1000. In addition, approximately 2% to 50% of patients with skeletal fractures will develop an infection, one of the causes of disordered bone healing. Dysfunction of bone marrow mesenchymal stem cells (BMSCs) plays a key role in disordered bone repair. However, the specific mechanisms underlying BMSC dysfunction caused by bone infection are largely unknown. In this study, we discovered that Fibulin2 expression was upregulated in infected bone tissues and that BMSCs were the source of infection-induced Fibulin2. Importantly, Fibulin2 knockout accelerated mineralized bone formation during skeletal development and inhibited inflammatory bone resorption. We demonstrated that Fibulin2 suppressed BMSC osteogenic differentiation by binding to Notch2 and inactivating the Notch2 signaling pathway. Moreover, Fibulin2 knockdown restored Notch2 pathway activation and promoted BMSC osteogenesis; these outcomes were abolished by DAPT, a Notch inhibitor. Furthermore, transplanted Fibulin2 knockdown BMSCs displayed better bone repair potential in vivo. Altogether, Fibulin2 is a negative regulator of BMSC osteogenic differentiation that inhibits osteogenesis by inactivating the Notch2 signaling pathway in infected bone.
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spelling pubmed-99817002023-03-04 Fibulin2: a negative regulator of BMSC osteogenic differentiation in infected bone fracture healing Li, Shi-Dan Xing, Wei Wang, Shao-Chuan Li, You-Bin Jiang, Hao Zheng, Han-Xuan Li, Xiao-Ming Yang, Jing Guo, De-Bin Xie, Xiao-Yu Jiang, Ren-Qing Fan, Chao Li, Lei Xu, Xiang Fei, Jun Exp Mol Med Article Bone fracture remains a common occurrence, with a population-weighted incidence of approximately 3.21 per 1000. In addition, approximately 2% to 50% of patients with skeletal fractures will develop an infection, one of the causes of disordered bone healing. Dysfunction of bone marrow mesenchymal stem cells (BMSCs) plays a key role in disordered bone repair. However, the specific mechanisms underlying BMSC dysfunction caused by bone infection are largely unknown. In this study, we discovered that Fibulin2 expression was upregulated in infected bone tissues and that BMSCs were the source of infection-induced Fibulin2. Importantly, Fibulin2 knockout accelerated mineralized bone formation during skeletal development and inhibited inflammatory bone resorption. We demonstrated that Fibulin2 suppressed BMSC osteogenic differentiation by binding to Notch2 and inactivating the Notch2 signaling pathway. Moreover, Fibulin2 knockdown restored Notch2 pathway activation and promoted BMSC osteogenesis; these outcomes were abolished by DAPT, a Notch inhibitor. Furthermore, transplanted Fibulin2 knockdown BMSCs displayed better bone repair potential in vivo. Altogether, Fibulin2 is a negative regulator of BMSC osteogenic differentiation that inhibits osteogenesis by inactivating the Notch2 signaling pathway in infected bone. Nature Publishing Group UK 2023-02-17 /pmc/articles/PMC9981700/ /pubmed/36797542 http://dx.doi.org/10.1038/s12276-023-00942-0 Text en © Crown 2023 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
Li, Shi-Dan
Xing, Wei
Wang, Shao-Chuan
Li, You-Bin
Jiang, Hao
Zheng, Han-Xuan
Li, Xiao-Ming
Yang, Jing
Guo, De-Bin
Xie, Xiao-Yu
Jiang, Ren-Qing
Fan, Chao
Li, Lei
Xu, Xiang
Fei, Jun
Fibulin2: a negative regulator of BMSC osteogenic differentiation in infected bone fracture healing
title Fibulin2: a negative regulator of BMSC osteogenic differentiation in infected bone fracture healing
title_full Fibulin2: a negative regulator of BMSC osteogenic differentiation in infected bone fracture healing
title_fullStr Fibulin2: a negative regulator of BMSC osteogenic differentiation in infected bone fracture healing
title_full_unstemmed Fibulin2: a negative regulator of BMSC osteogenic differentiation in infected bone fracture healing
title_short Fibulin2: a negative regulator of BMSC osteogenic differentiation in infected bone fracture healing
title_sort fibulin2: a negative regulator of bmsc osteogenic differentiation in infected bone fracture healing
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9981700/
https://www.ncbi.nlm.nih.gov/pubmed/36797542
http://dx.doi.org/10.1038/s12276-023-00942-0
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