Cargando…

Single-Cell RNA Sequencing Reveals B Cells Are Important Regulators in Fracture Healing

The bone marrow microenvironment is composed primarily of immune and stromal cells that play important roles in fracture healing. Although immune cells have been identified in mouse bone marrow, variations in their numbers and type during the fracture healing process remain poorly defined. In this s...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Hao, Wang, Renkai, Wang, Guangchao, Zhang, Bo, Wang, Chao, Li, Di, Ding, Chen, Wei, Qiang, Fan, Zhenyu, Tang, Hao, Ji, Fang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8606664/
https://www.ncbi.nlm.nih.gov/pubmed/34819916
http://dx.doi.org/10.3389/fendo.2021.666140
_version_ 1784602380975734784
author Zhang, Hao
Wang, Renkai
Wang, Guangchao
Zhang, Bo
Wang, Chao
Li, Di
Ding, Chen
Wei, Qiang
Fan, Zhenyu
Tang, Hao
Ji, Fang
author_facet Zhang, Hao
Wang, Renkai
Wang, Guangchao
Zhang, Bo
Wang, Chao
Li, Di
Ding, Chen
Wei, Qiang
Fan, Zhenyu
Tang, Hao
Ji, Fang
author_sort Zhang, Hao
collection PubMed
description The bone marrow microenvironment is composed primarily of immune and stromal cells that play important roles in fracture healing. Although immune cells have been identified in mouse bone marrow, variations in their numbers and type during the fracture healing process remain poorly defined. In this study, single-cell RNA sequencing was used to identify immune cells in fracture tissues, including neutrophils, monocytes, T cells, B cells, and plasma cells. The number of B cells decreased significantly in the early stage of fracture healing. Furthermore, B cells in mice fracture models decreased significantly during the epiphyseal phase and then gradually returned to normal during the epiphyseal transformation phase of fracture healing. The B-cell pattern was opposite to that of bone formation and resorption activities. Notably, B-cell–derived exosomes inhibited bone homeostasis in fracture healing. In humans, a decrease in the number of B cells during the epiphyseal phase stimulated fracture healing. Then, as the numbers of osteoblasts increased during the callus reconstruction stage, the number of B cells gradually recovered, which reduced additional bone regeneration. Thus, B cells are key regulators of fracture healing and inhibit excessive bone regeneration by producing multiple osteoblast inhibitors.
format Online
Article
Text
id pubmed-8606664
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-86066642021-11-23 Single-Cell RNA Sequencing Reveals B Cells Are Important Regulators in Fracture Healing Zhang, Hao Wang, Renkai Wang, Guangchao Zhang, Bo Wang, Chao Li, Di Ding, Chen Wei, Qiang Fan, Zhenyu Tang, Hao Ji, Fang Front Endocrinol (Lausanne) Endocrinology The bone marrow microenvironment is composed primarily of immune and stromal cells that play important roles in fracture healing. Although immune cells have been identified in mouse bone marrow, variations in their numbers and type during the fracture healing process remain poorly defined. In this study, single-cell RNA sequencing was used to identify immune cells in fracture tissues, including neutrophils, monocytes, T cells, B cells, and plasma cells. The number of B cells decreased significantly in the early stage of fracture healing. Furthermore, B cells in mice fracture models decreased significantly during the epiphyseal phase and then gradually returned to normal during the epiphyseal transformation phase of fracture healing. The B-cell pattern was opposite to that of bone formation and resorption activities. Notably, B-cell–derived exosomes inhibited bone homeostasis in fracture healing. In humans, a decrease in the number of B cells during the epiphyseal phase stimulated fracture healing. Then, as the numbers of osteoblasts increased during the callus reconstruction stage, the number of B cells gradually recovered, which reduced additional bone regeneration. Thus, B cells are key regulators of fracture healing and inhibit excessive bone regeneration by producing multiple osteoblast inhibitors. Frontiers Media S.A. 2021-11-08 /pmc/articles/PMC8606664/ /pubmed/34819916 http://dx.doi.org/10.3389/fendo.2021.666140 Text en Copyright © 2021 Zhang, Wang, Wang, Zhang, Wang, Li, Ding, Wei, Fan, Tang and Ji 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
Zhang, Hao
Wang, Renkai
Wang, Guangchao
Zhang, Bo
Wang, Chao
Li, Di
Ding, Chen
Wei, Qiang
Fan, Zhenyu
Tang, Hao
Ji, Fang
Single-Cell RNA Sequencing Reveals B Cells Are Important Regulators in Fracture Healing
title Single-Cell RNA Sequencing Reveals B Cells Are Important Regulators in Fracture Healing
title_full Single-Cell RNA Sequencing Reveals B Cells Are Important Regulators in Fracture Healing
title_fullStr Single-Cell RNA Sequencing Reveals B Cells Are Important Regulators in Fracture Healing
title_full_unstemmed Single-Cell RNA Sequencing Reveals B Cells Are Important Regulators in Fracture Healing
title_short Single-Cell RNA Sequencing Reveals B Cells Are Important Regulators in Fracture Healing
title_sort single-cell rna sequencing reveals b cells are important regulators in fracture healing
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8606664/
https://www.ncbi.nlm.nih.gov/pubmed/34819916
http://dx.doi.org/10.3389/fendo.2021.666140
work_keys_str_mv AT zhanghao singlecellrnasequencingrevealsbcellsareimportantregulatorsinfracturehealing
AT wangrenkai singlecellrnasequencingrevealsbcellsareimportantregulatorsinfracturehealing
AT wangguangchao singlecellrnasequencingrevealsbcellsareimportantregulatorsinfracturehealing
AT zhangbo singlecellrnasequencingrevealsbcellsareimportantregulatorsinfracturehealing
AT wangchao singlecellrnasequencingrevealsbcellsareimportantregulatorsinfracturehealing
AT lidi singlecellrnasequencingrevealsbcellsareimportantregulatorsinfracturehealing
AT dingchen singlecellrnasequencingrevealsbcellsareimportantregulatorsinfracturehealing
AT weiqiang singlecellrnasequencingrevealsbcellsareimportantregulatorsinfracturehealing
AT fanzhenyu singlecellrnasequencingrevealsbcellsareimportantregulatorsinfracturehealing
AT tanghao singlecellrnasequencingrevealsbcellsareimportantregulatorsinfracturehealing
AT jifang singlecellrnasequencingrevealsbcellsareimportantregulatorsinfracturehealing