Journal Article

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

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

2025

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: 60 APPLIED LIFE SCIENCES / Animals / Anterior cruciate ligament / Antibodies / Apoptosis / Arthritis / biological and medical sciences / Cartilage / Cartilage diseases / Cell activation / Connective tissue diseases / Connective tissues / Crack initiation / flow cytometry / Fractures / gene expression / Gene sequencing / Genotype & phenotype / immune cells / Immune system / Inflammation / Inflammatory response / Injuries / Joint and ligament injuries / Joint diseases / Knee / Knee Injuries - complications / Knee Injuries - metabolism / Knee Injuries - pathology / Knee Joint - metabolism / Knee Joint - pathology / knee joints / Lectins, C-Type - genetics / Lectins, C-Type - metabolism / Macrophages / Macrophages - metabolism / Male / Mannose Receptor / Mannose-Binding Lectins - metabolism / Membrane Glycoproteins - genetics / Membrane Glycoproteins - metabolism / Meniscus / Mice / Mice, Inbred C57BL / Mice, Inbred MRL lpr / Monocytes / neutrophils / Osteoarthritis / Osteoarthritis - etiology / Osteoarthritis - metabolism / Osteoarthritis - pathology / Pathogenesis / Populations / Receptors, Cell Surface - genetics / Receptors, Cell Surface - metabolism / Receptors, Immunologic - genetics / Receptors, Immunologic - metabolism / skeletal joints / Subpopulations / Synovial joints