CD206+ Trem2+ macrophage accumulation in the murine knee joint after injury is associated with protection against post-traumatic osteoarthritis in MRL/MpJ mice.

Post-traumatic osteoarthritis (PTOA) is a painful joint disease characterized by the degradation of bone, cartilage, and other connective tissues in the joint. PTOA is initiated by trauma to joint-stabilizing tissues, such as the anterior cruciate ligament, medial meniscus, or by intra-articular fra...

Full description

Saved in:
Bibliographic Details
Main Authors: Jillian L McCool, Aimy Sebastian, Nicholas R Hum, Stephen P Wilson, Oscar A Davalos, Deepa K Murugesh, Beheshta Amiri, Cesar Morfin, Blaine A Christiansen, Gabriela G Loots
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0312587
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1841555609871187968
author Jillian L McCool
Aimy Sebastian
Nicholas R Hum
Stephen P Wilson
Oscar A Davalos
Deepa K Murugesh
Beheshta Amiri
Cesar Morfin
Blaine A Christiansen
Gabriela G Loots
author_facet Jillian L McCool
Aimy Sebastian
Nicholas R Hum
Stephen P Wilson
Oscar A Davalos
Deepa K Murugesh
Beheshta Amiri
Cesar Morfin
Blaine A Christiansen
Gabriela G Loots
author_sort Jillian L McCool
collection DOAJ
description Post-traumatic osteoarthritis (PTOA) is a painful joint disease characterized by the degradation of bone, cartilage, and other connective tissues in the joint. PTOA is initiated by trauma to joint-stabilizing tissues, such as the anterior cruciate ligament, medial meniscus, or by intra-articular fractures. In humans, ~50% of joint injuries progress to PTOA, while the rest spontaneously resolve. To better understand molecular programs contributing to PTOA development or resolution, we examined injury-induced fluctuations in immune cell populations and transcriptional shifts by single-cell RNA sequencing of synovial joints in PTOA-susceptible C57BL/6J (B6) and PTOA-resistant MRL/MpJ (MRL) mice. We identified significant differences in monocyte and macrophage subpopulations between MRL and B6 joints. A potent myeloid-driven anti-inflammatory response was observed in MRL injured joints that significantly contrasted the pro-inflammatory signaling seen in B6 joints. Multiple CD206+ macrophage populations classically described as M2 were found enriched in MRL injured joints. These CD206+ macrophages also robustly expressed Trem2, a receptor involved in inflammation and myeloid cell activation. These data suggest that the PTOA resistant MRL mouse strain displays an enhanced capacity of clearing debris and apoptotic cells induced by inflammation after injury due to an increase in activated M2 macrophages within the synovial tissue and joint space.
format Article
id doaj-art-7db79302895d4237bf78f131841a017c
institution Kabale University
issn 1932-6203
language English
publishDate 2025-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj-art-7db79302895d4237bf78f131841a017c2025-01-08T05:31:48ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01201e031258710.1371/journal.pone.0312587CD206+ Trem2+ macrophage accumulation in the murine knee joint after injury is associated with protection against post-traumatic osteoarthritis in MRL/MpJ mice.Jillian L McCoolAimy SebastianNicholas R HumStephen P WilsonOscar A DavalosDeepa K MurugeshBeheshta AmiriCesar MorfinBlaine A ChristiansenGabriela G LootsPost-traumatic osteoarthritis (PTOA) is a painful joint disease characterized by the degradation of bone, cartilage, and other connective tissues in the joint. PTOA is initiated by trauma to joint-stabilizing tissues, such as the anterior cruciate ligament, medial meniscus, or by intra-articular fractures. In humans, ~50% of joint injuries progress to PTOA, while the rest spontaneously resolve. To better understand molecular programs contributing to PTOA development or resolution, we examined injury-induced fluctuations in immune cell populations and transcriptional shifts by single-cell RNA sequencing of synovial joints in PTOA-susceptible C57BL/6J (B6) and PTOA-resistant MRL/MpJ (MRL) mice. We identified significant differences in monocyte and macrophage subpopulations between MRL and B6 joints. A potent myeloid-driven anti-inflammatory response was observed in MRL injured joints that significantly contrasted the pro-inflammatory signaling seen in B6 joints. Multiple CD206+ macrophage populations classically described as M2 were found enriched in MRL injured joints. These CD206+ macrophages also robustly expressed Trem2, a receptor involved in inflammation and myeloid cell activation. These data suggest that the PTOA resistant MRL mouse strain displays an enhanced capacity of clearing debris and apoptotic cells induced by inflammation after injury due to an increase in activated M2 macrophages within the synovial tissue and joint space.https://doi.org/10.1371/journal.pone.0312587
spellingShingle Jillian L McCool
Aimy Sebastian
Nicholas R Hum
Stephen P Wilson
Oscar A Davalos
Deepa K Murugesh
Beheshta Amiri
Cesar Morfin
Blaine A Christiansen
Gabriela G Loots
CD206+ Trem2+ macrophage accumulation in the murine knee joint after injury is associated with protection against post-traumatic osteoarthritis in MRL/MpJ mice.
PLoS ONE
title CD206+ Trem2+ macrophage accumulation in the murine knee joint after injury is associated with protection against post-traumatic osteoarthritis in MRL/MpJ mice.
title_full CD206+ Trem2+ macrophage accumulation in the murine knee joint after injury is associated with protection against post-traumatic osteoarthritis in MRL/MpJ mice.
title_fullStr CD206+ Trem2+ macrophage accumulation in the murine knee joint after injury is associated with protection against post-traumatic osteoarthritis in MRL/MpJ mice.
title_full_unstemmed CD206+ Trem2+ macrophage accumulation in the murine knee joint after injury is associated with protection against post-traumatic osteoarthritis in MRL/MpJ mice.
title_short CD206+ Trem2+ macrophage accumulation in the murine knee joint after injury is associated with protection against post-traumatic osteoarthritis in MRL/MpJ mice.
title_sort cd206 trem2 macrophage accumulation in the murine knee joint after injury is associated with protection against post traumatic osteoarthritis in mrl mpj mice
url https://doi.org/10.1371/journal.pone.0312587
work_keys_str_mv AT jillianlmccool cd206trem2macrophageaccumulationinthemurinekneejointafterinjuryisassociatedwithprotectionagainstposttraumaticosteoarthritisinmrlmpjmice
AT aimysebastian cd206trem2macrophageaccumulationinthemurinekneejointafterinjuryisassociatedwithprotectionagainstposttraumaticosteoarthritisinmrlmpjmice
AT nicholasrhum cd206trem2macrophageaccumulationinthemurinekneejointafterinjuryisassociatedwithprotectionagainstposttraumaticosteoarthritisinmrlmpjmice
AT stephenpwilson cd206trem2macrophageaccumulationinthemurinekneejointafterinjuryisassociatedwithprotectionagainstposttraumaticosteoarthritisinmrlmpjmice
AT oscaradavalos cd206trem2macrophageaccumulationinthemurinekneejointafterinjuryisassociatedwithprotectionagainstposttraumaticosteoarthritisinmrlmpjmice
AT deepakmurugesh cd206trem2macrophageaccumulationinthemurinekneejointafterinjuryisassociatedwithprotectionagainstposttraumaticosteoarthritisinmrlmpjmice
AT beheshtaamiri cd206trem2macrophageaccumulationinthemurinekneejointafterinjuryisassociatedwithprotectionagainstposttraumaticosteoarthritisinmrlmpjmice
AT cesarmorfin cd206trem2macrophageaccumulationinthemurinekneejointafterinjuryisassociatedwithprotectionagainstposttraumaticosteoarthritisinmrlmpjmice
AT blaineachristiansen cd206trem2macrophageaccumulationinthemurinekneejointafterinjuryisassociatedwithprotectionagainstposttraumaticosteoarthritisinmrlmpjmice
AT gabrielagloots cd206trem2macrophageaccumulationinthemurinekneejointafterinjuryisassociatedwithprotectionagainstposttraumaticosteoarthritisinmrlmpjmice