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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...

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Autores principales: Knights, Alexander J., Farrell, Easton C., Ellis, Olivia M., Song, Michelle J., Appleton, C. Thomas, Maerz, Tristan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
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.
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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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