{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T19:24:13Z","timestamp":1793993053460,"version":"4.8.0"},"reference-count":90,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T00:00:00Z","timestamp":1735862400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Defense Awards","award":["PR180268"],"award-info":[{"award-number":["PR180268"]}]},{"name":"Department of Defense Awards","award":["PR192271"],"award-info":[{"award-number":["PR192271"]}]},{"name":"Department of Defense Awards","award":["PR180268P1"],"award-info":[{"award-number":["PR180268P1"]}]},{"name":"National Institute of Health","award":["R01 AR075013"],"award-info":[{"award-number":["R01 AR075013"]}]},{"DOI":"10.13039\/100006227","name":"Lawrence Livermore National Laboratory","doi-asserted-by":"publisher","award":["LDRD 20-LW-002"],"award-info":[{"award-number":["LDRD 20-LW-002"]}],"id":[{"id":"10.13039\/100006227","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    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\n                    <jats:sup>+<\/jats:sup>\n                    macrophage populations classically described as M2 were found enriched in MRL injured joints. These CD206\n                    <jats:sup>+<\/jats:sup>\n                    macrophages also robustly expressed\n                    <jats:italic>Trem2<\/jats:italic>\n                    , 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.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0312587","type":"journal-article","created":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T13:34:15Z","timestamp":1735911255000},"page":"e0312587","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["CD206+ Trem2+ macrophage accumulation in the murine knee joint after injury is associated with protection against post-traumatic osteoarthritis in MRL\/MpJ mice"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5317-8764","authenticated-orcid":true,"given":"Jillian L.","family":"McCool","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aimy","family":"Sebastian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas R.","family":"Hum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen P.","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar A.","family":"Davalos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepa K.","family":"Murugesh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beheshta","family":"Amiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesar","family":"Morfin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0105-6458","authenticated-orcid":true,"given":"Blaine A.","family":"Christiansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9546-5561","authenticated-orcid":true,"given":"Gabriela G.","family":"Loots","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,1,3]]},"reference":[{"issue":"4","key":"pone.0312587.ref001","doi-asserted-by":"crossref","DOI":"10.3390\/ijms22041996","article-title":"An Evidence-Based Systematic Review of Human Knee Post-Traumatic Osteoarthritis (PTOA): Timeline of Clinical Presentation and Disease Markers, Comparison of Knee Joint PTOA Models and Early Disease Implications.","volume":"22","author":"CM Khella","year":"2021","journal-title":"Int J Mol Sci."},{"issue":"6","key":"pone.0312587.ref002","doi-asserted-by":"crossref","first-page":"491","DOI":"10.4085\/1062-6050-51.5.08","article-title":"Epidemiology of Posttraumatic Osteoarthritis.","volume":"52","author":"AC Thomas","year":"2017","journal-title":"J Athl Train."},{"issue":"2","key":"pone.0312587.ref003","doi-asserted-by":"crossref","first-page":"e000279","DOI":"10.1136\/rmdopen-2016-000279","article-title":"Post-traumatic arthritis: overview on pathogenic mechanisms and role of inflammation","volume":"2","author":"L Punzi","year":"2016","journal-title":"RMD Open"},{"issue":"6","key":"pone.0312587.ref004","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1007\/s11515-012-1192-4","article-title":"The super super-healing MRL mouse strain.","volume":"7","author":"A. Heydemann","year":"2012","journal-title":"Front Biol (Beijing)."},{"issue":"11","key":"pone.0312587.ref005","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1016\/j.joca.2008.03.014","article-title":"Evidence for articular cartilage regeneration in MRL\/MpJ mice","volume":"16","author":"J Fitzgerald","year":"2008","journal-title":"Osteoarthritis Cartilage"},{"issue":"1","key":"pone.0312587.ref006","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1006\/clin.1998.4519","article-title":"A new murine model for mammalian wound repair and regeneration","volume":"88","author":"LD Clark","year":"1998","journal-title":"Clin Immunol Immunopathol"},{"issue":"4","key":"pone.0312587.ref007","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1016\/j.bbrc.2016.03.149","article-title":"Superior angiogenesis facilitates digit regrowth in MRL\/MpJ mice compared to C57BL\/6 mice","volume":"473","author":"A Kwiatkowski","year":"2016","journal-title":"Biochem Biophys Res Commun"},{"issue":"11","key":"pone.0312587.ref008","doi-asserted-by":"crossref","first-page":"2229","DOI":"10.1002\/jbmr.4117","article-title":"LPS-Induced Inflammation Prior to Injury Exacerbates the Development of Post-Traumatic Osteoarthritis in Mice","volume":"35","author":"ME Mendez","year":"2020","journal-title":"J Bone Miner Res"},{"key":"pone.0312587.ref009","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.matbio.2014.08.011","article-title":"Regeneration of articular cartilage in healer and non-healer mice","volume":"39","author":"MF Rai","year":"2014","journal-title":"Matrix Biol"},{"issue":"2","key":"pone.0312587.ref010","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1002\/dvdy.10242","article-title":"Regeneration of the ear after wounding in different mouse strains is dependent on the severity of wound trauma","volume":"226","author":"C Rajnoch","year":"2003","journal-title":"Dev Dyn"},{"issue":"9","key":"pone.0312587.ref011","doi-asserted-by":"crossref","DOI":"10.3390\/ijms19092657","article-title":"Comparative Transcriptomics Identifies Novel Genes and Pathways Involved in Post-Traumatic Osteoarthritis Development and Progression.","volume":"19","author":"A Sebastian","year":"2018","journal-title":"Int J Mol Sci"},{"issue":"3","key":"pone.0312587.ref012","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1002\/art.23288","article-title":"Absence of posttraumatic arthritis following intraarticular fracture in the MRL\/MpJ mouse","volume":"58","author":"BD Ward","year":"2008","journal-title":"Arthritis Rheum"},{"issue":"3","key":"pone.0312587.ref013","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1136\/ard-2023-224907","article-title":"OA susceptibility in mice is partially mediated by the gut microbiome, is transferrable via microbiome transplantation and is associated with immunophenotype changes","volume":"83","author":"E Prinz","year":"2024","journal-title":"Ann Rheum Dis"},{"issue":"8","key":"pone.0312587.ref014","doi-asserted-by":"crossref","first-page":"8809","DOI":"10.1096\/fj.201802132RR","article-title":"Characterization of articular cartilage homeostasis and the mechanism of superior cartilage regeneration of MRL\/MpJ mice","volume":"33","author":"Z Deng","year":"2019","journal-title":"FASEB J"},{"issue":"3","key":"pone.0312587.ref015","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1002\/art.37796","article-title":"Genetic and cellular evidence of decreased inflammation associated with reduced incidence of posttraumatic arthritis in MRL\/MpJ mice","volume":"65","author":"JS Lewis","year":"2013","journal-title":"Arthritis Rheum"},{"issue":"15","key":"pone.0312587.ref016","doi-asserted-by":"crossref","DOI":"10.3390\/ijms22158005","article-title":"Anti-Inflammatory Therapeutic Approaches to Prevent or Delay Post-Traumatic Osteoarthritis (PTOA) of the Knee Joint with a Focus on Sustained Delivery Approaches.","volume":"22","author":"CM Khella","year":"2021","journal-title":"Int J Mol Sci."},{"issue":"6","key":"pone.0312587.ref017","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1002\/jor.21359","article-title":"Post-traumatic osteoarthritis: improved understanding and opportunities for early intervention","volume":"29","author":"DD Anderson","year":"2011","journal-title":"J Orthop Res"},{"issue":"8","key":"pone.0312587.ref018","doi-asserted-by":"crossref","first-page":"722","DOI":"10.2460\/ajvr.75.8.722","article-title":"Concentrations of stromal cell-derived factor-1 in serum, plasma, and synovial fluid of horses with osteochondral injury","volume":"75","author":"DC Dymock","year":"2014","journal-title":"Am J Vet Res"},{"issue":"1","key":"pone.0312587.ref019","first-page":"8","article-title":"Expression of interleukin-8 and intercellular cell adhesion molecule-1 in the synovial membrane and cranial cruciate ligament of dogs after rupture of the ligament","volume":"76","author":"M El-Hadi","year":"2012","journal-title":"Can J Vet Res"},{"key":"pone.0312587.ref020","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.exger.2014.03.010","article-title":"Influence of age on osteoarthritis progression after anterior cruciate ligament transection in rats","volume":"55","author":"ML Ferr\u00e1ndiz","year":"2014","journal-title":"Exp Gerontol"},{"issue":"10","key":"pone.0312587.ref021","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1089\/hum.2012.189","article-title":"Lentiviral small hairpin RNA knockdown of macrophage inflammatory protein-1\u03b3 ameliorates experimentally induced osteoarthritis in mice","volume":"24","author":"PC Shen","year":"2013","journal-title":"Hum Gene Ther"},{"issue":"1","key":"pone.0312587.ref022","doi-asserted-by":"crossref","first-page":"e54633","DOI":"10.1371\/journal.pone.0054633","article-title":"Disease progression and phasic changes in gene expression in a mouse model of osteoarthritis","volume":"8","author":"RF Loeser","year":"2013","journal-title":"PLoS One"},{"issue":"1","key":"pone.0312587.ref023","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1186\/s13075-021-02661-1","article-title":"Immune cell profiles in synovial fluid after anterior cruciate ligament and meniscus injuries","volume":"23","author":"SY Kim-Wang","year":"2021","journal-title":"Arthritis Res Ther"},{"issue":"3","key":"pone.0312587.ref024","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.clim.2012.12.011","article-title":"Immunopathogenesis of osteoarthritis","volume":"146","author":"A Haseeb","year":"2013","journal-title":"Clin Immunol"},{"issue":"7771","key":"pone.0312587.ref025","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1038\/s41586-019-1471-1","article-title":"Locally renewing resident synovial macrophages provide a protective barrier for the joint","volume":"572","author":"S Culemann","year":"2019","journal-title":"Nature"},{"issue":"7760","key":"pone.0312587.ref026","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1038\/s41586-019-1263-7","article-title":"Distinct fibroblast subsets drive inflammation and damage in arthritis","volume":"570","author":"AP Croft","year":"2019","journal-title":"Nature"},{"issue":"8","key":"pone.0312587.ref027","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/nrrheum.2017.115","article-title":"Synovial tissue research: a state-of-the-art review.","volume":"13","author":"C Orr","year":"2017","journal-title":"Nat Rev Rheumatol"},{"key":"pone.0312587.ref028","doi-asserted-by":"crossref","first-page":"862161","DOI":"10.3389\/fmed.2022.862161","article-title":"Synovial Macrophage and Fibroblast Heterogeneity in Joint Homeostasis and Inflammation.","volume":"9","author":"K Knab","year":"2022","journal-title":"Front Med (Lausanne)."},{"issue":"3","key":"pone.0312587.ref029","doi-asserted-by":"crossref","first-page":"281","DOI":"10.2174\/1568010054022024","article-title":"Macrophages in inflammation","volume":"4","author":"N Fujiwara","year":"2005","journal-title":"Curr Drug Targets Inflamm Allergy"},{"issue":"7","key":"pone.0312587.ref030","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/j.bbadis.2012.12.001","article-title":"Macrophages and fibrosis: How resident and infiltrating mononuclear phagocytes orchestrate all phases of tissue injury and repair","volume":"1832","author":"M Lech","year":"2013","journal-title":"Biochim Biophys Acta"},{"issue":"2","key":"pone.0312587.ref031","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1002\/reg2.77","article-title":"Macrophages and fibroblasts during inflammation and tissue repair in models of organ regeneration","volume":"4","author":"AL Mescher","year":"2017","journal-title":"Regeneration (Oxf)."},{"key":"pone.0312587.ref032","doi-asserted-by":"crossref","first-page":"938075","DOI":"10.3389\/fimmu.2022.938075","article-title":"Single-cell RNA-Seq reveals changes in immune landscape in post-traumatic osteoarthritis.","volume":"13","author":"A Sebastian","year":"2022","journal-title":"Front Immunol."},{"key":"pone.0312587.ref033","doi-asserted-by":"crossref","first-page":"419","DOI":"10.3389\/fphys.2018.00419","article-title":"The Role of Macrophages in Acute and Chronic Wound Healing and Interventions to Promote Pro-wound Healing Phenotypes.","volume":"9","author":"P Krzyszczyk","year":"2018","journal-title":"Front Physiol."},{"issue":"5","key":"pone.0312587.ref034","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.jcyt.2020.02.003","article-title":"Mesenchymal stromal cells from dermal and adipose tissues induce macrophage polarization to a pro-repair phenotype and improve skin wound healing.","volume":"22","author":"HD Zomer","year":"2020","journal-title":"Cytotherapy"},{"issue":"6","key":"pone.0312587.ref035","doi-asserted-by":"crossref","DOI":"10.3390\/cells10061462","article-title":"Single-Cell RNA-Seq Reveals Transcriptomic Heterogeneity and Post-Traumatic Osteoarthritis-Associated Early Molecular Changes in Mouse Articular Chondrocytes.","volume":"10","author":"A Sebastian","year":"2021","journal-title":"Cells"},{"issue":"10","key":"pone.0312587.ref036","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1016\/j.joca.2015.05.009","article-title":"Non-invasive mouse models of post-traumatic osteoarthritis","volume":"23","author":"BA Christiansen","year":"2015","journal-title":"Osteoarthritis Cartilage"},{"issue":"3","key":"pone.0312587.ref037","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1002\/jor.23263","article-title":"Global molecular changes in a tibial compression induced ACL rupture model of post-traumatic osteoarthritis","volume":"35","author":"JC Chang","year":"2017","journal-title":"J Orthop Res"},{"issue":"1","key":"pone.0312587.ref038","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1002\/jor.22480","article-title":"Comparison of loading rate-dependent injury modes in a murine model of post-traumatic osteoarthritis","volume":"32","author":"KA Lockwood","year":"2014","journal-title":"J Orthop Res"},{"issue":"7","key":"pone.0312587.ref039","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1016\/j.joca.2012.04.014","article-title":"Musculoskeletal changes following non-invasive knee injury using a novel mouse model of post-traumatic osteoarthritis","volume":"20","author":"BA Christiansen","year":"2012","journal-title":"Osteoarthritis Cartilage"},{"key":"pone.0312587.ref040","first-page":"9050754","article-title":"Evaluation of Decalcification Techniques for Rat Femurs Using HE and Immunohistochemical Staining","volume":"2017","author":"H Liu","year":"2017","journal-title":"Biomed Res Int"},{"issue":"7","key":"pone.0312587.ref041","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH Image to ImageJ: 25 years of image analysis.","volume":"9","author":"CA Schneider","year":"2012","journal-title":"Nat Methods."},{"key":"pone.0312587.ref042","first-page":"18","article-title":"The OARSI histopathology initiative\u2014recommendations for histological assessments of osteoarthritis in the mouse","volume":"3","author":"SS Glasson","year":"2010","journal-title":"Osteoarthritis Cartilage"},{"issue":"13","key":"pone.0312587.ref043","doi-asserted-by":"crossref","first-page":"3573","DOI":"10.1016\/j.cell.2021.04.048","article-title":"Integrated analysis of multimodal single-cell data","volume":"184","author":"Y Hao","year":"2021","journal-title":"Cell"},{"issue":"12","key":"pone.0312587.ref044","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1038\/s41592-019-0619-0","article-title":"Fast, sensitive and accurate integration of single-cell data with Harmony.","volume":"16","author":"I Korsunsky","year":"2019","journal-title":"Nat Methods."},{"issue":"3","key":"pone.0312587.ref045","first-page":"100141","article-title":"clusterProfiler 4.0: A universal enrichment tool for interpreting omics data","volume":"2","author":"T Wu","year":"2021","journal-title":"Innovation (Camb)."},{"issue":"13","key":"pone.0312587.ref046","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1093\/bioinformatics\/btl140","article-title":"Improved scoring of functional groups from gene expression data by decorrelating GO graph structure","volume":"22","author":"A Alexa","year":"2006","journal-title":"Bioinformatics"},{"issue":"Web Server issue","key":"pone.0312587.ref047","doi-asserted-by":"crossref","first-page":"W305","DOI":"10.1093\/nar\/gkp427","article-title":"ToppGene Suite for gene list enrichment analysis and candidate gene prioritization","volume":"37","author":"J Chen","year":"2009","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"pone.0312587.ref048","doi-asserted-by":"crossref","first-page":"vbac016","DOI":"10.1093\/bioadv\/vbac016","article-title":"decoupleR: ensemble of computational methods to infer biological activities from omics data","volume":"2","author":"IMP Badia","year":"2022","journal-title":"Bioinform Adv"},{"key":"pone.0312587.ref049","article-title":"Generating publication ready visualizations for Single Cell transcriptomics using SCpubr","author":"E. Blanco-Carmona","year":"2022","journal-title":"bioRxiv"},{"key":"pone.0312587.ref050","author":"N. Frerebeau","year":"2024","journal-title":"Colour Schemes for Scientific Data Visualization"},{"issue":"43","key":"pone.0312587.ref051","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.21105\/joss.01686","article-title":"Welcome to the Tidyverse.","volume":"4","author":"H Wickham","year":"2019","journal-title":"Journal of Open Source Software"},{"issue":"10","key":"pone.0312587.ref052","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1038\/nmeth.4402","article-title":"Reversed graph embedding resolves complex single-cell trajectories.","volume":"14","author":"X Qiu","year":"2017","journal-title":"Nat Methods."},{"issue":"3","key":"pone.0312587.ref053","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1002\/jor.23343","article-title":"Using mouse models to investigate the pathophysiology, treatment, and prevention of post-traumatic osteoarthritis","volume":"35","author":"CL Blaker","year":"2017","journal-title":"J Orthop Res"},{"issue":"1","key":"pone.0312587.ref054","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s00005-017-0476-4","article-title":"Heterogeneity Among Neutrophils.","volume":"66","author":"M Garley","year":"2018","journal-title":"Arch Immunol Ther Exp (Warsz)."},{"issue":"1","key":"pone.0312587.ref055","doi-asserted-by":"crossref","first-page":"2856","DOI":"10.1038\/s41467-021-22973-9","article-title":"The neutrotime transcriptional signature defines a single continuum of neutrophils across biological compartments.","volume":"12","author":"R Grieshaber-Bouyer","year":"2021","journal-title":"Nat Commun."},{"issue":"1","key":"pone.0312587.ref056","doi-asserted-by":"crossref","first-page":"3874","DOI":"10.1038\/s41467-023-39601-3","article-title":"Author Correction: Endogenous IL-1 receptor antagonist restricts healthy and malignant myeloproliferation","volume":"14","author":"A Villatoro","year":"2023","journal-title":"Nat Commun"},{"issue":"6","key":"pone.0312587.ref057","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1016\/j.immuni.2016.12.001","article-title":"The Heterogeneity of Ly6C(hi) Monocytes Controls Their Differentiation into iNOS(+) Macrophages or Monocyte-Derived Dendritic Cells.","volume":"45","author":"S Menezes","year":"2016","journal-title":"Immunity"},{"issue":"6","key":"pone.0312587.ref058","article-title":"Pancreatic cancer is marked by complement-high blood monocytes and tumor-associated macrophages","volume":"4","author":"SB Kemp","year":"2021","journal-title":"Life Sci Alliance"},{"issue":"20","key":"pone.0312587.ref059","doi-asserted-by":"crossref","first-page":"E3954","DOI":"10.1073\/pnas.1616417114","article-title":"Pre\/pro-B cells generate macrophage populations during homeostasis and inflammation","volume":"114","author":"T Audzevich","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"3","key":"pone.0312587.ref060","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1084\/jem.20160844","article-title":"Soluble TREM2 induces inflammatory responses and enhances microglial survival","volume":"214","author":"L Zhong","year":"2017","journal-title":"J Exp Med"},{"issue":"43","key":"pone.0312587.ref061","doi-asserted-by":"crossref","first-page":"11138","DOI":"10.1523\/JNEUROSCI.1238-16.2016","article-title":"TREM2\/DAP12 Signal Elicits Proinflammatory Response in Microglia and Exacerbates Neuropathic Pain","volume":"36","author":"M Kobayashi","year":"2016","journal-title":"J Neurosci"},{"issue":"8","key":"pone.0312587.ref062","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1038\/s41591-020-0939-8","article-title":"Distinct synovial tissue macrophage subsets regulate inflammation and remission in rheumatoid arthritis","volume":"26","author":"S Alivernini","year":"2020","journal-title":"Nat Med"},{"issue":"9","key":"pone.0312587.ref063","first-page":"e117","article-title":"Caveolin-1 plays a critical role in the differentiation of monocytes into macrophages","volume":"32","author":"Y Fu","year":"2012","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"8","key":"pone.0312587.ref064","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1093\/cvr\/cvac161","article-title":"Integrated single-cell analysis-based classification of vascular mononuclear phagocytes in mouse and human atherosclerosis","volume":"119","author":"A Zernecke","year":"2023","journal-title":"Cardiovasc Res"},{"issue":"67","key":"pone.0312587.ref065","doi-asserted-by":"crossref","first-page":"eabf7777","DOI":"10.1126\/sciimmunol.abf7777","article-title":"Three tissue resident macrophage subsets coexist across organs with conserved origins and life cycles.","volume":"7","author":"SA Dick","year":"2022","journal-title":"Sci Immunol."},{"issue":"6432","key":"pone.0312587.ref066","doi-asserted-by":"crossref","DOI":"10.1126\/science.aau0964","article-title":"Two distinct interstitial macrophage populations coexist across tissues in specific subtissular niches","volume":"363","author":"S Chakarov","year":"2019","journal-title":"Science"},{"issue":"1","key":"pone.0312587.ref067","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/s41590-018-0272-2","article-title":"Self-renewing resident cardiac macrophages limit adverse remodeling following myocardial infarction","volume":"20","author":"SA Dick","year":"2019","journal-title":"Nat Immunol"},{"key":"pone.0312587.ref068","article-title":"Synovial macrophage diversity and activation of M-CSF signaling in post-traumatic osteoarthritis.","author":"AJ Knights","year":"2023","journal-title":"bioRxiv."},{"issue":"15","key":"pone.0312587.ref069","doi-asserted-by":"crossref","first-page":"24840","DOI":"10.18632\/oncotarget.15266","article-title":"HIF1\/2alpha mediates hypoxia-induced LDHA expression in human pancreatic cancer cells","volume":"8","author":"XG Cui","year":"2017","journal-title":"Oncotarget"},{"issue":"2","key":"pone.0312587.ref070","doi-asserted-by":"crossref","first-page":"e0147961","DOI":"10.1371\/journal.pone.0147961","article-title":"Up-Regulation of ENO1 by HIF-1alpha in Retinal Pigment Epithelial Cells after Hypoxic Challenge Is Not Involved in the Regulation of VEGF Secretion.","volume":"11","author":"F Zheng","year":"2016","journal-title":"PLoS One."},{"issue":"1","key":"pone.0312587.ref071","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1080\/21655979.2021.1903207","article-title":"Combining bulk and single-cell RNA-sequencing data to reveal gene expression pattern of chondrocytes in the osteoarthritic knee","volume":"12","author":"X Li","year":"2021","journal-title":"Bioengineered"},{"issue":"11","key":"pone.0312587.ref072","article-title":"Single-Cell RNA-Sequencing Identifies Infrapatellar Fat Pad Macrophage Polarization in Acute Synovitis\/Fat Pad Fibrosis and Cell Therapy.","volume":"8","author":"D Kouroupis","year":"2021","journal-title":"Bioengineering (Basel)."},{"issue":"1","key":"pone.0312587.ref073","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1002\/art.41486","article-title":"Synergistic Roles of Macrophages and Neutrophils in Osteoarthritis Progression.","volume":"73","author":"MF Hsueh","year":"2021","journal-title":"Arthritis Rheumatol."},{"issue":"11","key":"pone.0312587.ref074","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1016\/j.joca.2015.08.015","article-title":"Inflammation in joint injury and post-traumatic osteoarthritis","volume":"23","author":"J Lieberthal","year":"2015","journal-title":"Osteoarthritis Cartilage"},{"key":"pone.0312587.ref075","doi-asserted-by":"crossref","first-page":"763702","DOI":"10.3389\/fimmu.2021.763702","article-title":"Monocytes, Macrophages, and Their Potential Niches in Synovial Joints\u2014Therapeutic Targets in Post-Traumatic Osteoarthritis?","volume":"12","author":"P Haubruck","year":"2021","journal-title":"Front Immunol."},{"issue":"2","key":"pone.0312587.ref076","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.joca.2016.09.010","article-title":"The effects of different doses of IGF-1 on cartilage and subchondral bone during the repair of full-thickness articular cartilage defects in rabbits","volume":"25","author":"Z Zhang","year":"2017","journal-title":"Osteoarthritis Cartilage"},{"issue":"6","key":"pone.0312587.ref077","first-page":"4569","article-title":"Evaluation of the effects of the combination of BMP-2-modified BMSCs and PRP on cartilage defects.","volume":"16","author":"S Ruan","year":"2018","journal-title":"Exp Ther Med."},{"issue":"13","key":"pone.0312587.ref078","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.147413","article-title":"COVID-19 and RA share an SPP1 myeloid pathway that drives PD-L1+ neutrophils and CD14+ monocytes.","volume":"6","author":"L MacDonald","year":"2021","journal-title":"JCI Insight."},{"key":"pone.0312587.ref079","doi-asserted-by":"crossref","first-page":"616044","DOI":"10.3389\/fimmu.2020.616044","article-title":"Trem-2 Promotes Emergence of Restorative Macrophages and Endothelial Cells During Recovery From Hepatic Tissue Damage.","volume":"11","author":"I Coelho","year":"2020","journal-title":"Front Immunol."},{"issue":"3","key":"pone.0312587.ref080","doi-asserted-by":"crossref","first-page":"e21417","DOI":"10.1096\/fj.202001970R","article-title":"Single-cell RNA sequencing reveals the induction of novel myeloid and myeloid-associated cell populations in visceral fat with long-term obesity","volume":"35","author":"NS Harasymowicz","year":"2021","journal-title":"Faseb j"},{"issue":"1","key":"pone.0312587.ref081","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s13024-022-00542-y","article-title":"TREM2 in the pathogenesis of AD: a lipid metabolism regulator and potential metabolic therapeutic target","volume":"17","author":"RY Li","year":"2022","journal-title":"Mol Neurodegener"},{"issue":"2","key":"pone.0312587.ref082","doi-asserted-by":"crossref","first-page":"112131","DOI":"10.1016\/j.celrep.2023.112131","article-title":"Platelet-instructed SPP1(+) macrophages drive myofibroblast activation in fibrosis in a CXCL4-dependent manner.","volume":"42","author":"K Hoeft","year":"2023","journal-title":"Cell Rep"},{"issue":"7","key":"pone.0312587.ref083","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1038\/cr.2015.68","article-title":"Metabolic reprogramming in macrophages and dendritic cells in innate immunity","volume":"25","author":"B Kelly","year":"2015","journal-title":"Cell Res"},{"issue":"7783","key":"pone.0312587.ref084","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1038\/s41586-019-1631-3","article-title":"Resolving the fibrotic niche of human liver cirrhosis at single-cell level","volume":"575","author":"P Ramachandran","year":"2019","journal-title":"Nature"},{"issue":"3","key":"pone.0312587.ref085","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1002\/JLB.3A0520-745RR","article-title":"Classically activated mouse macrophages produce methylglyoxal that induces a TLR4- and RAGE-independent proinflammatory response","volume":"109","author":"D Prantner","year":"2021","journal-title":"J Leukoc Biol"},{"issue":"7","key":"pone.0312587.ref086","article-title":"Chromosome-Level Analysis of the Pelochelys cantorii Genome Provides Insights to Its Immunity, Growth and Longevity.","volume":"12","author":"X Liu","year":"2023","journal-title":"Biology (Basel)."},{"issue":"6","key":"pone.0312587.ref087","doi-asserted-by":"crossref","first-page":"109965","DOI":"10.1016\/j.celrep.2021.109965","article-title":"Genomic expansion of Aldh1a1 protects beavers against high metabolic aldehydes from lipid oxidation","volume":"37","author":"Q Zhang","year":"2021","journal-title":"Cell Rep"},{"issue":"4","key":"pone.0312587.ref088","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1111\/j.1755-148X.2012.01018.x","article-title":"Breast cancer suppressor candidate-1 (BCSC-1) is a melanoma tumor suppressor that down regulates MITF.","volume":"25","author":"SI Anghel","year":"2012","journal-title":"Pigment Cell Melanoma Res."},{"key":"pone.0312587.ref089","doi-asserted-by":"crossref","first-page":"101509","DOI":"10.1016\/j.smim.2021.101509","article-title":"Functions of macrophage colony-stimulating factor (CSF1) in development, homeostasis, and tissue repair.","volume":"54","author":"A Sehgal","year":"2021","journal-title":"Semin Immunol."},{"key":"pone.0312587.ref090","doi-asserted-by":"crossref","first-page":"764621","DOI":"10.1155\/2012\/764621","article-title":"A review of translational animal models for knee osteoarthritis.","volume":"2012","author":"MH Gregory","year":"2012","journal-title":"Arthritis"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0312587","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T13:34:45Z","timestamp":1735911285000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0312587"}},"subtitle":[],"editor":[{"given":"Zhiwen","family":"Luo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,1,3]]},"references-count":90,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1,3]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0312587","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,3]]}}}