Cargando…

Circulating Monocytes Act as a Common Trigger for the Calcification Paradox of Osteoporosis and Carotid Atherosclerosis via TGFB1-SP1 and TNFSF10-NFKB1 Axis

BACKGROUND: Osteoporosis often occurs with carotid atherosclerosis and causes contradictory calcification across tissue in the same patient, which is called the “calcification paradox”. Circulating monocytes may be responsible for this unbalanced ectopic calcification. Here, we aimed to show how CD1...

Descripción completa

Detalles Bibliográficos
Autores principales: Zeng, Ziliang, Guo, Rui, Wang, Zheyu, Yan, Haolin, Lv, Xin, Zhao, Qiancheng, Jiang, Xu, Zhang, Chi, Zhang, Di, Yang, Canchun, Li, Wenpeng, Zhang, Zhilei, Wang, Qiwei, Huang, Renyuan, Li, Bo, Hu, Xumin, Gao, Liangbin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354531/
https://www.ncbi.nlm.nih.gov/pubmed/35937796
http://dx.doi.org/10.3389/fendo.2022.944751
_version_ 1784763093381808128
author Zeng, Ziliang
Guo, Rui
Wang, Zheyu
Yan, Haolin
Lv, Xin
Zhao, Qiancheng
Jiang, Xu
Zhang, Chi
Zhang, Di
Yang, Canchun
Li, Wenpeng
Zhang, Zhilei
Wang, Qiwei
Huang, Renyuan
Li, Bo
Hu, Xumin
Gao, Liangbin
author_facet Zeng, Ziliang
Guo, Rui
Wang, Zheyu
Yan, Haolin
Lv, Xin
Zhao, Qiancheng
Jiang, Xu
Zhang, Chi
Zhang, Di
Yang, Canchun
Li, Wenpeng
Zhang, Zhilei
Wang, Qiwei
Huang, Renyuan
Li, Bo
Hu, Xumin
Gao, Liangbin
author_sort Zeng, Ziliang
collection PubMed
description BACKGROUND: Osteoporosis often occurs with carotid atherosclerosis and causes contradictory calcification across tissue in the same patient, which is called the “calcification paradox”. Circulating monocytes may be responsible for this unbalanced ectopic calcification. Here, we aimed to show how CD14(+) monocytes contribute to the pathophysiology of coexisting postmenopausal osteoporosis and carotid atherosclerosis. METHODS: We comprehensively analyzed osteoporosis data from the mRNA array dataset GSE56814 and the scRNA-seq dataset GSM4423510. Carotid atherosclerosis data were obtained from the GSE23746 mRNA dataset and GSM4705591 scRNA-seq dataset. First, osteoblast and vascular SMC lineages were annotated based on their functional expression using gene set enrichment analysis and AUCell scoring. Next, pseudotime analysis was applied to draw their differentiated trajectory and identify the key gene expression changes in crossroads. Then, ligand–receptor interactions between CD14(+) monocytes and osteoblast and vascular smooth muscle cell (SMC) lineages were annotated with iTALK. Finally, we selected calcification paradox-related expression in circulating monocytes with LASSO analysis. RESULTS: First, we found a large proportion of delayed premature osteoblasts in osteoporosis and osteogenic SMCs in atherosclerosis. Second, CD14(+) monocytes interacted with the intermediate cells of the premature osteoblast and osteogenic SMC lineage by delivering TGFB1 and TNFSF10. This interaction served as a trigger activating the transcription factors (TF) SP1 and NFKB1 to upregulate the inflammatory response and cell senescence and led to a retarded premature state in the osteoblast lineage and osteogenic transition in the SMC lineage. Then, 76.49% of common monocyte markers were upregulated in the circulating monocytes between the two diseases, which were related to chemotaxis and inflammatory responses. Finally, we identified 7 calcification paradox-related genes on circulating monocytes, which were upregulated in aging cells and downregulated in DNA repair cells, indicating that the aging monocytes contributed to the development of the two diseases. CONCLUSIONS: Our work provides a perspective for understanding the triggering roles of CD14(+) monocytes in the development of the calcification paradox in osteoporosis- and atherosclerosis-related cells based on combined scRNA and mRNA data. This study provided us with an elucidation of the mechanisms underlying the calcification paradox and could help in developing preventive and therapeutic strategies.
format Online
Article
Text
id pubmed-9354531
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-93545312022-08-06 Circulating Monocytes Act as a Common Trigger for the Calcification Paradox of Osteoporosis and Carotid Atherosclerosis via TGFB1-SP1 and TNFSF10-NFKB1 Axis Zeng, Ziliang Guo, Rui Wang, Zheyu Yan, Haolin Lv, Xin Zhao, Qiancheng Jiang, Xu Zhang, Chi Zhang, Di Yang, Canchun Li, Wenpeng Zhang, Zhilei Wang, Qiwei Huang, Renyuan Li, Bo Hu, Xumin Gao, Liangbin Front Endocrinol (Lausanne) Endocrinology BACKGROUND: Osteoporosis often occurs with carotid atherosclerosis and causes contradictory calcification across tissue in the same patient, which is called the “calcification paradox”. Circulating monocytes may be responsible for this unbalanced ectopic calcification. Here, we aimed to show how CD14(+) monocytes contribute to the pathophysiology of coexisting postmenopausal osteoporosis and carotid atherosclerosis. METHODS: We comprehensively analyzed osteoporosis data from the mRNA array dataset GSE56814 and the scRNA-seq dataset GSM4423510. Carotid atherosclerosis data were obtained from the GSE23746 mRNA dataset and GSM4705591 scRNA-seq dataset. First, osteoblast and vascular SMC lineages were annotated based on their functional expression using gene set enrichment analysis and AUCell scoring. Next, pseudotime analysis was applied to draw their differentiated trajectory and identify the key gene expression changes in crossroads. Then, ligand–receptor interactions between CD14(+) monocytes and osteoblast and vascular smooth muscle cell (SMC) lineages were annotated with iTALK. Finally, we selected calcification paradox-related expression in circulating monocytes with LASSO analysis. RESULTS: First, we found a large proportion of delayed premature osteoblasts in osteoporosis and osteogenic SMCs in atherosclerosis. Second, CD14(+) monocytes interacted with the intermediate cells of the premature osteoblast and osteogenic SMC lineage by delivering TGFB1 and TNFSF10. This interaction served as a trigger activating the transcription factors (TF) SP1 and NFKB1 to upregulate the inflammatory response and cell senescence and led to a retarded premature state in the osteoblast lineage and osteogenic transition in the SMC lineage. Then, 76.49% of common monocyte markers were upregulated in the circulating monocytes between the two diseases, which were related to chemotaxis and inflammatory responses. Finally, we identified 7 calcification paradox-related genes on circulating monocytes, which were upregulated in aging cells and downregulated in DNA repair cells, indicating that the aging monocytes contributed to the development of the two diseases. CONCLUSIONS: Our work provides a perspective for understanding the triggering roles of CD14(+) monocytes in the development of the calcification paradox in osteoporosis- and atherosclerosis-related cells based on combined scRNA and mRNA data. This study provided us with an elucidation of the mechanisms underlying the calcification paradox and could help in developing preventive and therapeutic strategies. Frontiers Media S.A. 2022-07-22 /pmc/articles/PMC9354531/ /pubmed/35937796 http://dx.doi.org/10.3389/fendo.2022.944751 Text en Copyright © 2022 Zeng, Guo, Wang, Yan, Lv, Zhao, Jiang, Zhang, Zhang, Yang, Li, Zhang, Wang, Huang, Li, Hu and Gao https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Zeng, Ziliang
Guo, Rui
Wang, Zheyu
Yan, Haolin
Lv, Xin
Zhao, Qiancheng
Jiang, Xu
Zhang, Chi
Zhang, Di
Yang, Canchun
Li, Wenpeng
Zhang, Zhilei
Wang, Qiwei
Huang, Renyuan
Li, Bo
Hu, Xumin
Gao, Liangbin
Circulating Monocytes Act as a Common Trigger for the Calcification Paradox of Osteoporosis and Carotid Atherosclerosis via TGFB1-SP1 and TNFSF10-NFKB1 Axis
title Circulating Monocytes Act as a Common Trigger for the Calcification Paradox of Osteoporosis and Carotid Atherosclerosis via TGFB1-SP1 and TNFSF10-NFKB1 Axis
title_full Circulating Monocytes Act as a Common Trigger for the Calcification Paradox of Osteoporosis and Carotid Atherosclerosis via TGFB1-SP1 and TNFSF10-NFKB1 Axis
title_fullStr Circulating Monocytes Act as a Common Trigger for the Calcification Paradox of Osteoporosis and Carotid Atherosclerosis via TGFB1-SP1 and TNFSF10-NFKB1 Axis
title_full_unstemmed Circulating Monocytes Act as a Common Trigger for the Calcification Paradox of Osteoporosis and Carotid Atherosclerosis via TGFB1-SP1 and TNFSF10-NFKB1 Axis
title_short Circulating Monocytes Act as a Common Trigger for the Calcification Paradox of Osteoporosis and Carotid Atherosclerosis via TGFB1-SP1 and TNFSF10-NFKB1 Axis
title_sort circulating monocytes act as a common trigger for the calcification paradox of osteoporosis and carotid atherosclerosis via tgfb1-sp1 and tnfsf10-nfkb1 axis
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354531/
https://www.ncbi.nlm.nih.gov/pubmed/35937796
http://dx.doi.org/10.3389/fendo.2022.944751
work_keys_str_mv AT zengziliang circulatingmonocytesactasacommontriggerforthecalcificationparadoxofosteoporosisandcarotidatherosclerosisviatgfb1sp1andtnfsf10nfkb1axis
AT guorui circulatingmonocytesactasacommontriggerforthecalcificationparadoxofosteoporosisandcarotidatherosclerosisviatgfb1sp1andtnfsf10nfkb1axis
AT wangzheyu circulatingmonocytesactasacommontriggerforthecalcificationparadoxofosteoporosisandcarotidatherosclerosisviatgfb1sp1andtnfsf10nfkb1axis
AT yanhaolin circulatingmonocytesactasacommontriggerforthecalcificationparadoxofosteoporosisandcarotidatherosclerosisviatgfb1sp1andtnfsf10nfkb1axis
AT lvxin circulatingmonocytesactasacommontriggerforthecalcificationparadoxofosteoporosisandcarotidatherosclerosisviatgfb1sp1andtnfsf10nfkb1axis
AT zhaoqiancheng circulatingmonocytesactasacommontriggerforthecalcificationparadoxofosteoporosisandcarotidatherosclerosisviatgfb1sp1andtnfsf10nfkb1axis
AT jiangxu circulatingmonocytesactasacommontriggerforthecalcificationparadoxofosteoporosisandcarotidatherosclerosisviatgfb1sp1andtnfsf10nfkb1axis
AT zhangchi circulatingmonocytesactasacommontriggerforthecalcificationparadoxofosteoporosisandcarotidatherosclerosisviatgfb1sp1andtnfsf10nfkb1axis
AT zhangdi circulatingmonocytesactasacommontriggerforthecalcificationparadoxofosteoporosisandcarotidatherosclerosisviatgfb1sp1andtnfsf10nfkb1axis
AT yangcanchun circulatingmonocytesactasacommontriggerforthecalcificationparadoxofosteoporosisandcarotidatherosclerosisviatgfb1sp1andtnfsf10nfkb1axis
AT liwenpeng circulatingmonocytesactasacommontriggerforthecalcificationparadoxofosteoporosisandcarotidatherosclerosisviatgfb1sp1andtnfsf10nfkb1axis
AT zhangzhilei circulatingmonocytesactasacommontriggerforthecalcificationparadoxofosteoporosisandcarotidatherosclerosisviatgfb1sp1andtnfsf10nfkb1axis
AT wangqiwei circulatingmonocytesactasacommontriggerforthecalcificationparadoxofosteoporosisandcarotidatherosclerosisviatgfb1sp1andtnfsf10nfkb1axis
AT huangrenyuan circulatingmonocytesactasacommontriggerforthecalcificationparadoxofosteoporosisandcarotidatherosclerosisviatgfb1sp1andtnfsf10nfkb1axis
AT libo circulatingmonocytesactasacommontriggerforthecalcificationparadoxofosteoporosisandcarotidatherosclerosisviatgfb1sp1andtnfsf10nfkb1axis
AT huxumin circulatingmonocytesactasacommontriggerforthecalcificationparadoxofosteoporosisandcarotidatherosclerosisviatgfb1sp1andtnfsf10nfkb1axis
AT gaoliangbin circulatingmonocytesactasacommontriggerforthecalcificationparadoxofosteoporosisandcarotidatherosclerosisviatgfb1sp1andtnfsf10nfkb1axis