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Synovial macrophage diversity and activation of M-CSF signaling in post-traumatic osteoarthritis
OBJECTIVE: Synovium is home to immune and stromal cell types that orchestrate inflammation following a joint injury; in particular, macrophages are central protagonists in this process. We sought to define the cellular and temporal dynamics of the synovial immune niche in a mouse model of post-traum...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10592932/ https://www.ncbi.nlm.nih.gov/pubmed/37873464 http://dx.doi.org/10.1101/2023.10.03.559514 |
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author | Knights, Alexander J. Farrell, Easton C. Ellis, Olivia M. Song, Michelle J. Appleton, C. Thomas Maerz, Tristan |
author_facet | Knights, Alexander J. Farrell, Easton C. Ellis, Olivia M. Song, Michelle J. Appleton, C. Thomas Maerz, Tristan |
author_sort | Knights, Alexander J. |
collection | PubMed |
description | OBJECTIVE: Synovium is home to immune and stromal cell types that orchestrate inflammation following a joint injury; in particular, macrophages are central protagonists in this process. We sought to define the cellular and temporal dynamics of the synovial immune niche in a mouse model of post-traumatic osteoarthritis (PTOA), and to identify stromal-immune crosstalk mechanisms that coordinate macrophage function and phenotype. DESIGN: We induced PTOA in mice using a non-invasive tibial compression model of anterior cruciate ligament rupture (ACLR). Single cell RNA-seq and flow cytometry were used to assess immune cell populations in healthy (Sham) and injured (7d and 28d post-ACLR) synovium. Characterization of synovial macrophage polarization states was performed, alongside computational modeling of macrophage differentiation, as well as implicated transcriptional regulators and stromal-immune communication axes. RESULTS: Immune cell types are broadly represented in healthy synovium, but experience drastic expansion and speciation in PTOA, most notably in the macrophage portion. We identified several polarization states of macrophages in synovium following joint injury, underpinned by distinct transcriptomic signatures, and regulated in part by stromal-derived macrophage colony-stimulating factor signaling. The transcription factors Pu.1, Cebpα, Cebpβ, and Jun were predicted to control differentiation of systemically derived monocytes into pro-inflammatory synovial macrophages. CONCLUSIONS: We defined different synovial macrophage subpopulations present in healthy and injured mouse synovium. Nuanced characterization of the distinct functions, origins, and disease kinetics of macrophage subtypes in PTOA will be critical for targeting these highly versatile cells for therapeutic purposes. |
format | Online Article Text |
id | pubmed-10592932 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-105929322023-10-24 Synovial macrophage diversity and activation of M-CSF signaling in post-traumatic osteoarthritis Knights, Alexander J. Farrell, Easton C. Ellis, Olivia M. Song, Michelle J. Appleton, C. Thomas Maerz, Tristan bioRxiv Article OBJECTIVE: Synovium is home to immune and stromal cell types that orchestrate inflammation following a joint injury; in particular, macrophages are central protagonists in this process. We sought to define the cellular and temporal dynamics of the synovial immune niche in a mouse model of post-traumatic osteoarthritis (PTOA), and to identify stromal-immune crosstalk mechanisms that coordinate macrophage function and phenotype. DESIGN: We induced PTOA in mice using a non-invasive tibial compression model of anterior cruciate ligament rupture (ACLR). Single cell RNA-seq and flow cytometry were used to assess immune cell populations in healthy (Sham) and injured (7d and 28d post-ACLR) synovium. Characterization of synovial macrophage polarization states was performed, alongside computational modeling of macrophage differentiation, as well as implicated transcriptional regulators and stromal-immune communication axes. RESULTS: Immune cell types are broadly represented in healthy synovium, but experience drastic expansion and speciation in PTOA, most notably in the macrophage portion. We identified several polarization states of macrophages in synovium following joint injury, underpinned by distinct transcriptomic signatures, and regulated in part by stromal-derived macrophage colony-stimulating factor signaling. The transcription factors Pu.1, Cebpα, Cebpβ, and Jun were predicted to control differentiation of systemically derived monocytes into pro-inflammatory synovial macrophages. CONCLUSIONS: We defined different synovial macrophage subpopulations present in healthy and injured mouse synovium. Nuanced characterization of the distinct functions, origins, and disease kinetics of macrophage subtypes in PTOA will be critical for targeting these highly versatile cells for therapeutic purposes. Cold Spring Harbor Laboratory 2023-10-05 /pmc/articles/PMC10592932/ /pubmed/37873464 http://dx.doi.org/10.1101/2023.10.03.559514 Text en https://creativecommons.org/licenses/by-nd/4.0/This work is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, and only so long as attribution is given to the creator. The license allows for commercial use. |
spellingShingle | Article Knights, Alexander J. Farrell, Easton C. Ellis, Olivia M. Song, Michelle J. Appleton, C. Thomas Maerz, Tristan Synovial macrophage diversity and activation of M-CSF signaling in post-traumatic osteoarthritis |
title | Synovial macrophage diversity and activation of M-CSF signaling in post-traumatic osteoarthritis |
title_full | Synovial macrophage diversity and activation of M-CSF signaling in post-traumatic osteoarthritis |
title_fullStr | Synovial macrophage diversity and activation of M-CSF signaling in post-traumatic osteoarthritis |
title_full_unstemmed | Synovial macrophage diversity and activation of M-CSF signaling in post-traumatic osteoarthritis |
title_short | Synovial macrophage diversity and activation of M-CSF signaling in post-traumatic osteoarthritis |
title_sort | synovial macrophage diversity and activation of m-csf signaling in post-traumatic osteoarthritis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10592932/ https://www.ncbi.nlm.nih.gov/pubmed/37873464 http://dx.doi.org/10.1101/2023.10.03.559514 |
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