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

McCool, Jillian L.; Sebastian, Aimy; Hum, Nicholas R.; Wilson, Stephen P.; Davalos, Oscar A.; Murugesh, Deepa K.; Amiri, Beheshta; Morfin, Cesar; Christiansen, Blaine A.; Loots, Gabriela G.

doi:10.1371/journal.pone.0312587

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

Journal Article · Fri Jan 03 00:00:00 EST 2025 · PLoS ONE

DOI:https://doi.org/10.1371/journal.pone.0312587· OSTI ID:2532502

^[1]; Sebastian, Aimy ^[2]; Hum, Nicholas R. ^[2]; Wilson, Stephen P. ^[2]; Davalos, Oscar A. ^[2]; Murugesh, Deepa K. ^[2]; Amiri, Beheshta ^[2]; Morfin, Cesar ^[3]; ^[4]; ^[5]

Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States); Univ. of California, Merced, CA (United States)
Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)
Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States); University of California Davis Health, Sacramento, CA (United States)
University of California Davis Health, Sacramento, CA (United States)
Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States); Univ. of California, Merced, CA (United States); University of California Davis Health, Sacramento, CA (United States)

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.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)

Sponsoring Organization:: USDOE National Nuclear Security Administration (NNSA)

Grant/Contract Number:: AC52-07NA27344

OSTI ID:: 2532502

Report Number(s):: LLNL--JRNL-840836; 1062357

Journal Information:: PLoS ONE, Journal Name: PLoS ONE Journal Issue: 1 Vol. 20; ISSN 1932-6203

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: English

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Comparative Transcriptomics Identifies Novel Genes and Pathways Involved in Post-Traumatic Osteoarthritis Development and Progression

Journal Article · Thu Sep 06 20:00:00 EDT 2018 · International Journal of Molecular Sciences (Online) · OSTI ID:1476231

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60 APPLIED LIFE SCIENCES
Biological and medical sciences
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flow cytometry
gene expression
immune cells
knee joints
macrophages
monocytes
neutrophils
skeletal joints

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

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