M1 and M2 Monocytes in Rheumatoid Arthritis: A Contribution of Imbalance of M1/M2 Monocytes to Osteoclastogenesis

Objectives We investigated the relationships among M1 monocytes, M2 monocytes, osteoclast (OC) differentiation ability, and clinical characteristics in patients with rheumatoid arthritis (RA). Methods Peripheral blood mononuclear cells (PBMCs) were isolated from RA patients and healthy donors, and we then investigated the number of M1 monocytes or M2 monocytes by fluorescence-activated cell sorting. We also obtained and cultured CD14-positive cells from PBMCs from RA patients and healthy donors to investigate OC differentiation in vitro. Results Forty RA patients and 20 healthy donors were included. Twenty-two patients (55%) were anticitrullinated protein antibody (ACPA) positive. The median M1/M2 ratio was 0.59 (0.31–1.11, interquartile range). There were no significant differences between the RA patients and healthy donors. There was a positive correlation between the M1/M2 ratio and the differentiated OC number in vitro in RA patients (ρ = 0.81, p < 0.001). The ACPA-positive patients had significantly higher M1/M2 ratios in vivo (p = 0.028) and significantly greater numbers of OCs in vitro (p = 0.005) than the ACPA-negative patients. Multivariable regression analysis revealed that the M1/M2 ratio was the sole significant contribution factor to in vitro osteoclastogenesis. RA patients with M1/M2 ratios >1 (having relatively more M1 monocytes) had higher C-reactive protein and erythrocyte sedimentation rates than RA patients with M1/M2 ratios ≤1. M1-dominant monocytes in vitro produced higher concentrations of interleukin-6 upon stimulation with lipopolysaccharide than M2 monocytes. Conclusion M1/M2 monocytes imbalance strongly contributes to osteoclastogenesis of RA patients. Our findings cast M1 and M2 monocyte subsets in a new light as a new target of treatments for RA to prevent progression of osteoclastic bone destruction.

• Publication year

  2018

• Venue

  Frontiers in Immunology

• Publication date

  2018-01-08

• Fields of study

  Medicine

• Identifiers
  DOI 10.3389/fimmu.2017.01958PMID 29375576PMCID 5766997
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• Monocytes with M1-dominant profiles produce higher interleukin-6 concentrations after lipopolysaccharide stimulation than M2 monocytes.

  Confidence 0.91

  박진우 (dztg5apj7m) extractionB (s683577b42) review--------- ✂ Cut Here ✂ --------- (jqthcshryb) review
• The M1/M2 ratio is the only significant predictor of in vitro osteoclastogenesis in the multivariable regression analysis.

  Confidence 0.93

  박진우 (dztg5apj7m) extractionB (s683577b42) review--------- ✂ Cut Here ✂ --------- (jqthcshryb) review
• ACPA-positive patients show higher in vivo M1/M2 ratios and greater in vitro osteoclastogenesis than ACPA-negative patients.

  Confidence 0.95

  박진우 (dztg5apj7m) extractionB (s683577b42) review--------- ✂ Cut Here ✂ --------- (jqthcshryb) review
• The M1/M2 monocyte ratio in rheumatoid arthritis correlates positively with the number of differentiated osteoclasts generated in vitro.

  Confidence 0.98

  박진우 (dztg5apj7m) extractionB (s683577b42) review--------- ✂ Cut Here ✂ --------- (jqthcshryb) review

• acpa positivity

  clinical characteristic, serostatus

  Anticitrullinated protein antibody status used to classify rheumatoid arthritis patients as antibody-positive or antibody-negative.

  Aliases: anticitrullinated protein antibody positivity, ACPA-positive status

  박진우 (dztg5apj7m) extractionB (s683577b42) review--------- ✂ Cut Here ✂ --------- (jqthcshryb) review
• interleukin-6

  cytokine, molecule

  A cytokine measured in culture supernatants after monocyte stimulation with lipopolysaccharide.

  Aliases: IL-6

  박진우 (dztg5apj7m) extractionB (s683577b42) review--------- ✂ Cut Here ✂ --------- (jqthcshryb) review
• lipopolysaccharide stimulation

  experimental condition, stimulation

  An ex vivo stimulation condition applied to monocytes to assess cytokine production.

  Aliases: LPS stimulation

  박진우 (dztg5apj7m) extractionB (s683577b42) review--------- ✂ Cut Here ✂ --------- (jqthcshryb) review
• m1/m2 ratio

  biomarker, ratio

  The measured ratio of M1 monocytes to M2 monocytes in peripheral blood mononuclear cells from the participants.

  Aliases: M1-to-M2 ratio, M1/M2 monocyte ratio

  박진우 (dztg5apj7m) extractionB (s683577b42) review--------- ✂ Cut Here ✂ --------- (jqthcshryb) review
• m1 monocytes

  cell subset, immune cell

  A pro-inflammatory monocyte subset quantified by fluorescence-activated cell sorting in peripheral blood mononuclear cells.

  Aliases: M1 monocyte subset

  박진우 (dztg5apj7m) extractionB (s683577b42) review--------- ✂ Cut Here ✂ --------- (jqthcshryb) review
• m2 monocytes

  cell subset, immune cell

  An anti-inflammatory monocyte subset quantified by fluorescence-activated cell sorting in peripheral blood mononuclear cells.

  Aliases: M2 monocyte subset

  박진우 (dztg5apj7m) extractionB (s683577b42) review--------- ✂ Cut Here ✂ --------- (jqthcshryb) review
• multivariable regression

  statistical method, analysis

  A statistical model used to evaluate which measured factors independently contributed to in vitro osteoclastogenesis.

  Aliases: multivariable regression analysis

  박진우 (dztg5apj7m) extractionB (s683577b42) review--------- ✂ Cut Here ✂ --------- (jqthcshryb) review
• osteoclast differentiation

  cellular process, assay outcome

  The in vitro generation of osteoclasts from CD14-positive cells cultured from participant peripheral blood mononuclear cells.

  Aliases: osteoclastogenesis, OC differentiation

  박진우 (dztg5apj7m) extractionB (s683577b42) review--------- ✂ Cut Here ✂ --------- (jqthcshryb) review
• rheumatoid arthritis

  condition, population

  The patient population from which peripheral blood mononuclear cells and clinical measurements were obtained.

  Aliases: RA

  박진우 (dztg5apj7m) extractionB (s683577b42) review--------- ✂ Cut Here ✂ --------- (jqthcshryb) review

• Among human macrophages polarised to different phenotypes, the M-CSF-oriented cells present the highest pro-inflammatory response to the rheumatoid arthritis-specific immune complexes containing ACPA

  2016cited by this paper
• Ontogeny and Polarization of Macrophages in Inflammation: Blood Monocytes Versus Tissue Macrophages

  2015cited by this paper
• Identification of a novel chemokine-dependent molecular mechanism underlying rheumatoid arthritis-associated autoantibody-mediated bone loss

  2015cited by this paper
• From Monocytes to M1/M2 Macrophages: Phenotypical vs. Functional Differentiation

  2014cited by this paper
• Pro-inflammatory monocyte-macrophage polarization imbalance in human hypercholesterolemia and atherosclerosis.

  2014cited by this paper
• Monocytes from Pregnant Women with Pre‐Eclampsia are Polarized to a M1 Phenotype

  2014cited by this paper
• An unbalanced monocyte polarisation in peripheral blood and bone marrow of patients with type 2 diabetes has an impact on microangiopathy

  2013cited by this paper
• Regression of Atherosclerosis Is Characterized by Broad Changes in the Plaque Macrophage Transcriptome

  2012cited by this paper
• Interleukin-6 receptor inhibition with tocilizumab and attainment of disease remission in rheumatoid arthritis: the role of acute-phase reactants.

  2011cited by this paper
• The increased in vitro osteoclastogenesis in patients with rheumatoid arthritis is due to increased percentage of precursors and decreased apoptosis - the In Vitro Osteoclast Differentiation in Arthritis (IODA) study.

  2011cited by this paper
• Rheumatoid arthritis classifi cation criteria : an American College of Rheumatology / European League Against Rheumatism collaborative initiative

  2010cited by this paper
• 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative.

  2010cited by this paper
• Nomenclature of monocytes and dendritic cells in blood.

  2010cited by this paper
• Smoking-Dependent Reprogramming of Alveolar Macrophage Polarization: Implication for Pathogenesis of Chronic Obstructive Pulmonary Disease1

  2009cited by this paper
• Alveolar macrophages in allergic asthma: An expression signature characterized by heat shock protein pathways

  2009cited by this paper
• Gene Expression Analysis of Macrophages That Facilitate Tumor Invasion Supports a Role for Wnt-Signaling in Mediating Their Activity in Primary Mammary Tumors

  2009cited by this paper
• Meta-analysis: Diagnostic Accuracy of Anti–Cyclic Citrullinated Peptide Antibody and Rheumatoid Factor for Rheumatoid Arthritis

  2008cited by this paper
• Macrophage activation and polarization.

  2008cited by this paper
• Meta-analysis: Diagnostic Accuracy of AntiCyclic Citrullinated Peptide Antibody and Rheumatoid Factor for Rheumatoid Arthritis

  2007cited by this paper
• The diagnostic significance of soluble CD163 and soluble interleukin-2 receptor alpha-chain in macrophage activation syndrome and untreated new-onset systemic juvenile idiopathic arthritis.

  2007cited by this paper
• Monocyte and macrophage heterogeneity

  2005influential reference
• Synovial tissue macrophages: a sensitive biomarker for response to treatment in patients with rheumatoid arthritis

  2004cited by this paper
• Hemoglobin Scavenger Receptor CD163 Mediates Interleukin-10 Release and Heme Oxygenase-1 Synthesis: Antiinflammatory Monocyte-Macrophage Responses In Vitro, in Resolving Skin Blisters In Vivo, and After Cardiopulmonary Bypass Surgery

  2004cited by this paper
• Alternative activation of macrophages

  2003cited by this paper
• High levels of osteoprotegerin and soluble receptor activator of nuclear factor kappa B ligand in serum of rheumatoid arthritis patients and their normalization after anti-tumor necrosis factor alpha treatment.

  2002influential reference
• Rheumatoid arthritis.

  2001cited by this paper
• Identification of cell types responsible for bone resorption in rheumatoid arthritis and juvenile rheumatoid arthritis.

  1998cited by this paper
• Interleukin‐6 and soluble interleukin‐6 receptors in the synovial fluids from rheumatoid arthritis patients are responsible for osteoclast‐like cell formation

  1996cited by this paper
• Symmetrical erosive peripheral polyarthritis in the Late Archaic Period of Alabama.

  1988cited by this paper
• [Rheumatoid arthritis].

  1983cited by this paper
• Therapeutic criteria in rheumatoid arthritis.

  1949cited by this paper

• Hydrogel microspheres loaded with sinomenine and Drynaria rhizome enhance the treatment of rheumatoid arthritis via immune regulation and promoting bone repair

  2026cites this paper
• Melatonin alleviates rheumatoid arthritis by promoting Src/Fundc1-mediated mitophagy to regulate macrophage polarization.

  2026cites this paper
• Exploring the Role of Macrophages and Their Associated Structures in Rheumatoid Arthritis

  2025cites this paper
• Identification and validation of immune-related biomarkers and polarization types of macrophages in keloid based on bulk RNA-seq and single-cell RNA-seq analysis.

  2025cites this paper
• Сhanges of the functional phenotype of circulating monocytes during pregnancy

  2025cites this paper
• Effect of amniotic fluid on hair follicle growth

  2025cites this paper
• Fluoxetine‐induced downregulation of circMap2k1 signaling cascade to improve neurological function after ischemic stroke

  2025cites this paper
• Immunomodulatory role of natural products in treating rheumatoid arthritis.

  2025cites this paper
• Targeted Infection Control and Tissue Integration via pH-Sensitive Smart Coatings on Implant Surfaces

  2025cites this paper
• Clinical and immunological features of PD-1 and Tim-3 expression on monocytes in axial spondyloarthritis

  2025cites this paper
• Investigation of the Effect and Mechanism of Fei Re Pu Qing Powder in Treating Acute Lung Injury (ALI) by Modulating Macrophage Polarization via Serum Pharmacology and Network Pharmacology.

  2025cites this paper
• Guardians on call: neutrophils, macrophages and dendritic cells in arthritis pathogenesis

  2025cites this paper
• Coelonin, an active component extract from Bletilla striata (Thunb.) Reichb.f., alleviates lipopolysaccharide-induced acute lung injury by increasing the expression of non-coding RNA Gm27505 and inhibiting the M1 polarization of macrophages caused by inflammatory responses.

  2025cites this paper
• Langerin+ Dendritic Cells in Cutaneous Fibrosis: The TGF-β1 Signaling Axis

  2025cites this paper
• Electroacupuncture attenuates bone erosion and promotes macrophage polarization in a mouse model of collagen-induced arthritis

  2025cites this paper
• Roles of Immunity and Endogenous Retroelements in the Pathogenesis of Rheumatoid Arthritis and Treatment Strategies

  2025cites this paper
• Cardiac Macrophages Promote Polarization of Macrophages toward M2 Phenotype to Improve Myocardial Remodeling via NGAL after Myocardial Infarction

  2025cites this paper
• Intracellular Calcium as a Regulator of Polarization and Target Reprogramming of Macrophages

  2025cites this paper
• Protective effect of lappaconitine on Freund's complete adjuvant-induced arthritis exerted through P2X7 receptor-mediated regulation of M1/M2 balance in rats.

  2025cites this paper
• Immunomodulatory effects of curcumin on macrophage polarization in rheumatoid arthritis

  2024cites this paper
• Wutou Decoction: A latest review on molecular mechanisms, clinical studies, quality control, pharmacokinetic studies, pharmacological effects, toxicity, and target prediction.

  2024cites this paper
• Emerging nanomedicines for macrophage-mediated cancer therapy.

  2024cites this paper
• Periplosides Extract from Cortex periplocae Improve Collagen Antibody-Induced Arthritis by Regulating Macrophage Polarization

  2024cites this paper
• Assessment of the Monocyte Subpopulations and M1/M2 Macrophage Ratio in Concentrated Bone Marrow Aspirate

  2024influential citation
• Role of Circulating Monocytes and Periodontopathic Bacteria in Pathophysiology of Rheumatoid Arthritis.

  2024cites this paper
• Retinoic acid ameliorates rheumatoid arthritis by attenuating inflammation and modulating macrophage polarization through MKP-1/MAPK signaling pathway

  2024cites this paper
• Macrophage‑driven pathogenesis in acute lung injury/acute respiratory disease syndrome: Harnessing natural products for therapeutic interventions (Review)

  2024cites this paper
• Contribution of macrophage polarization in bone metabolism: A literature review.

  2024cites this paper
• Case report: Single-cell RNA sequencing of PBMCs highlights monocyte gene expression alterations in a type A HBV-ACLF patient

  2024cites this paper
• The Contribution of Macrophage Plasticity to Inflammatory Arthritis and Their Potential as Therapeutic Targets

  2024influential citation
• Transcriptional Regulation and Function of Malic Enzyme 1 in Human Macrophage Activation

  2024cites this paper
• A novel inhibitor of class IIa histone deacetylases attenuates collagen‐induced arthritis

  2024cites this paper
• Targeting the serum marker interleukin 9 improves the underlying characterization and immune homeostasis in rheumatoid arthritis

  2024cites this paper
• Extracellular vesicles from a novel Lactiplantibacillus plantarum strain suppress inflammation and promote M2 macrophage polarization

  2024cites this paper
• Single-Cell Multi-Dimensional data analysis reveals the role of ARL4C in driving rheumatoid arthritis progression and Macrophage polarization dynamics.

  2024cites this paper
• Screening of Diagnostic Biomarkers and Immune Infiltration Characteristics Linking Rheumatoid Arthritis and Rosacea Based on Bioinformatics Analysis

  2024cites this paper
• EPSTI1 promotes osteoclast differentiation and bone resorption by PKR/NF-κB signaling.

  2024cites this paper
• Adipose-derived stem cell exosomes loaded with icariin alleviates rheumatoid arthritis by modulating macrophage polarization in rats

  2024cites this paper
• Potential use of stem cell therapies for treating osteoarthritis and rheumatoid arthritis

  2024cites this paper
• Inhibition of ferroptosis rescues M2 macrophages and alleviates arthritis by suppressing the HMGB1/TLR4/STAT3 axis in M1 macrophages

  2024cites this paper
• Exploration and validation of therapeutic molecules for rheumatoid arthritis based on ferroptosis-related genes.

  2024cites this paper
• Macrophage polarization in rheumatoid arthritis: signaling pathways, metabolic reprogramming, and crosstalk with synovial fibroblasts

  2024cites this paper
• Monocyte bioenergetics: An immunometabolic perspective in metabolic dysfunction-associated steatohepatitis

  2024cites this paper
• Rheumatoid arthritis-associated complications during pregnancy and its effect on offspring: comprehensive review

  2024cites this paper
• The monocyte cell surface is a unique site of autoantigen generation in rheumatoid arthritis

  2024cites this paper
• Deciphering the monocyte-targeting mechanisms of PEGylated cationic liposomes by investigating the biomolecular corona.

  2024cites this paper
• Small molecule α-methylene-γ-butyrolactone, an evolutionarily conserved moiety in sesquiterpene lactones, ameliorates arthritic phenotype via interference DNA binding activity of NF-κB

  2024cites this paper
• Role of macrophages and their exosomes in orthopedic diseases

  2024cites this paper
• The role of cardiac microenvironment in cardiovascular diseases: implications for therapy

  2024cites this paper
• Integrative analysis and validation of necroptosis-related molecular signature for evaluating diagnosis and immune features in Rheumatoid arthritis.

  2024cites this paper
• Exosomal Osteoclast-Derived miRNA in Rheumatoid Arthritis: From Their Pathogenesis in Bone Erosion to New Therapeutic Approaches

  2024cites this paper
• miR-345-3p Modulates M1/M2 Macrophage Polarization to Inhibit Inflammation in Bone Infection via Targeting MAP3K1 and NF-κB Pathway.

  2024cites this paper
• The promising role of tumor-associated macrophages in the treatment of cancer.

  2024cites this paper
• Macrophage-hitchhiking interleukin-10 plasmid DNA delivery system modulates rheumatoid arthritis microenvironment via the re-polarization of macrophages

  2024cites this paper
• Peripheral Immunophenotype in IgG4-Related Disease and Its Association with Clinical Phenotypes and Disease Activity

  2023cites this paper
• The Clinical Promise of Microalgae in Rheumatoid Arthritis: From Natural Compounds to Recombinant Therapeutics

  2023cites this paper
• Role of macrophages in the onset, maintenance, or control of arthritis caused by alphaviruses

  2023cites this paper
• Drug Repositioning of Metformin Encapsulated in PLGA Combined with Photothermal Therapy Ameliorates Rheumatoid Arthritis

  2023cites this paper
• Neglected immunoregulation: M2 polarization of macrophages triggered by low‐dose irradiation plays an important role in bone regeneration

  2023cites this paper
• Advancements in Macrophage-Targeted Drug Delivery for Effective Disease Management

  2023cites this paper
• Crosstalk between Sensory Neurons and Local Immunity during Peripheral Inflammation

  2023cites this paper
• Inhibition of Chitinase-3-like-1 expression by K284 ameliorates lipopolysaccharide-induced acute liver injury through down regulation of CXCL3

  2023cites this paper
• Exosomes derived from mesenchymal stem cells primed with disease-condition-serum improved therapeutic efficacy in a mouse rheumatoid arthritis model via enhanced TGF-β1 production

  2023cites this paper
• The Capacity of Magnesium to Induce Osteoclast Differentiation Is Greatly Enhanced by the Presence of Zoledronate

  2023cites this paper
• The Mechanisms and Efficacy of Photobiomodulation Therapy for Arthritis: A Comprehensive Review

  2023cites this paper
• Large-scale computational modelling of the M1 and M2 synovial macrophages in rheumatoid arthritis

  2023cites this paper
• The Effect of Amniotic Fluid On Haıir Follicle Growth

  2023cites this paper
• M1/M2 macrophages and their overlaps – myth or reality?

  2023cites this paper
• Management of Rheumatoid Arthritis: Possibilities and Challenges of Mesenchymal Stromal/Stem Cell-Based Therapies

  2023cites this paper
• The effects of IL-1β stimulated human umbilical cord mesenchymal stem cells on polarization and apoptosis of macrophages in rheumatoid arthritis

  2023cites this paper
• Guiqi Baizhu prescription ameliorates cytarabine-induced intestinal mucositis by targeting JAK2 to inhibit M1 macrophage polarization.

  2023cites this paper
• Exosomes from Cyclic Stretched Periodontal Ligament Cells Induced Periodontal Inflammation through miR-9-5p/SIRT1/NF-κB Signaling Pathway.

  2023cites this paper
• Characteristics, polarization and targeted therapy of mononuclear macrophages in rheumatoid arthritis.

  2023cites this paper
• circRNA_17725 Promotes Macrophage Polarization towards M2 by Targeting FAM46C to Alleviate Arthritis

  2023cites this paper
• Glycine protects against doxorubicin-induced heart toxicity in mice

  2023cites this paper
• An updated review of the immunological mechanisms of keloid scars

  2023cites this paper
• Microbe-Derived Antioxidants Alleviate Liver and Adipose Tissue Lipid Disorders and Metabolic Inflammation Induced by High Fat Diet in Mice

  2023cites this paper
• Exploring the effect of Er miao San-containing serum on macrophage polarization through miR-33/NLRP3 pathway.

  2023cites this paper
• Exploration of the mechanism by which Huangqi Guizhi Wuwu decoction inhibits Lps-induced inflammation by regulating macrophage polarization based on network pharmacology

  2023cites this paper
• Remodeling articular immune homeostasis with an efferocytosis-informed nanoimitator mitigates rheumatoid arthritis in mice

  2023cites this paper
• TiO2 nanostructured implant surface-mediated M2c polarization of inflammatory monocyte requiring intact cytoskeleton rearrangement

  2023cites this paper
• Role of C-reactive protein in disease progression, diagnosis and management

  2023cites this paper
• Peptidyl arginine deiminase expression and macrophage polarization following stimulation with citrullinated and malondialdehyde-acetaldehyde modified fibrinogen.

  2022cites this paper
• Nanoengineered therapy aiming at the etiology of rheumatoid arthritis

  2022cites this paper
• Rheumatoid Arthritis: Pathogenic Roles of Diverse Immune Cells

  2022cites this paper
• Accelerated Alveolar Bone Loss in a Mouse Model of Inflammatory Bowel Disease and its Relationship with Intestinal Inflammation.

  2022cites this paper
• Immunomodulatory matrix-bound nanovesicles mitigate acute and chronic pristane-induced rheumatoid arthritis

  2022cites this paper
• Leveraging Macrophages for Cancer Theranostics.

  2022cites this paper
• Macrophage-Associated Disorders: Pathophysiology, Treatment Challenges, and Possible Solutions

  2022cites this paper
• Bone erosion in inflammatory arthritis is attenuated by Trichinella spiralis through inhibiting M1 monocyte/macrophage polarization

  2022cites this paper
• Long Non-coding RNAs in Rheumatology.

  2022cites this paper
• Viewing keloids within the immune microenvironment.

  2022cites this paper
• Update on the role of extracellular vesicles in rheumatoid arthritis

  2022cites this paper
• Effects of different physical training protocols on inflammatory markers in Zymosan‐induced rheumatoid arthritis in Wistar rats

  2022cites this paper
• Polycyclic Aromatic Hydrocarbons Affect Rheumatoid Arthritis Pathogenesis via Aryl Hydrocarbon Receptor

  2022cites this paper
• Macrophage Dysfunction in Autoimmune Rheumatic Diseases and Atherosclerosis

  2022influential citation
• Immuno-modulating theranostic gold nanocages for the treatment of rheumatoid arthritis in vivo

  2022cites this paper
• The Role of M1/M2 Macrophage Polarization in Rheumatoid Arthritis Synovitis

  2022cites this paper
• Lymph Leakage Promotes Immunosuppression by Enhancing Anti-Inflammatory Macrophage Polarization

  2022cites this paper
• Cell-based therapies for rheumatoid arthritis: opportunities and challenges

  2022cites this paper