ArticleOsteoarthritis and cartilage2016
Direct in vivo evidence of activated macrophages in human osteoarthritis.
Article in Osteoarthritis and cartilage, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 198 papers, 4 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
198 citing papers in PubMed, 4 syntheses or guidelines pooled it, 325 citations in OpenAlex.
- Efficacy and immune-inflammatory mechanism of acupuncture-related therapy in animal models of knee osteoarthritis: a preclinical systematic review and network meta-analysis.Journal of orthopaedic surgery and research · 2024Pooled it
- Pooled it
- Phenotypic alteration of macrophages during osteoarthritis: a systematic review.Arthritis research & therapy · 2021Pooled it
- Increased lifespan, decreased mortality, and delayed cognitive decline in osteoarthritis.Scientific reports · 2019Pooled it
- Mechanistic Insights and Real-World Evidence of Autologous Protein Solution (APS) in Clinical Use.International journal of molecular sciences · 2025Trial
- Synovial fluid biomarkers associated with osteoarthritis severity reflect macrophage and neutrophil related inflammation.Arthritis research & therapy · 2019Trial
- Ameliorative effect of Gastrodia elata Blume extract on inflammation in a rat model of osteoarthritis.Laboratory animal research · 2026Article
- Article
- Mesenchymal stromal cells immunosuppress osteoarthritis synovial fluid modulated monocytes via IL-6 and CCL2.Cell death & disease · 2026Article
- A honeysuckle-decorated nanoimmunomodulator hijacks Macrophage-BMSC crosstalk to promote arthritic regeneration.Materials today. Bio · 2026Article
- Cellular Products with Anti-Inflammatory Properties for the Treatment of Cartilage Lesions.International journal of molecular sciences · 2026Review
- [The role and mechanism of chemokine network in promoting osteoarthritis progression by regulating synovial macrophage heterogeneity].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2026Review
- Targeting macrophages in OA nanomedicine: Therapeutic opportunity or delivery delusion? A pragmatic reappraisal.Asian journal of pharmaceutical sciences · 2026Article
- Integration of clinical features and metabolomics study reveals sex dimorphism in knee osteoarthritis.BMC musculoskeletal disorders · 2026Article
- Understanding the Inflammatory Aspect of Osteoarthritis: Lessons from Immune Checkpoint Inhibitors.Journal of clinical medicine · 2026Review
- Neuropeptide Y signaling in osteoarthritis pain: neuroimmune mechanisms, joint remodeling, and translational opportunities.Frontiers in pain research (Lausanne, Switzerland) · 2026Review
- The brain-gut-joint axis in arthritis: crosstalk, treatment, and future perspectives.Journal of orthopaedic translation · 2026Review
- Natural products and immune-cell responses in osteoarthritis: mechanisms, evidence maturity, and translational gaps.Frontiers in immunology · 2026Review
- Analysis of gut microbiota characteristics in osteoarthritis patients.Frontiers in cellular and infection microbiology · 2026Article
- Exosomes: critical mediator and therapeutic target for osteoarthritis.American journal of translational research · 2026Review
138 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveThrough binding to folate receptor-β (FR-β), the new (99m)Tc-EC20 (Etarfolatide) imaging technique detects activated but not resting macrophages in vivo. The goal of this study was to investigate macrophage-related inflammation in osteoarthritis (OA).
methodsTwenty-five individuals (50 knees) with symptomatic OA of at least one knee underwent SPECT-CT imaging of both knees and planar imaging of the whole body after injection of Etarfolatide. Scans and knee radiographs were scored blinded to clinical information including knee and other joint site pain severity. Measures of association controlled for age, gender, body mass index (BMI) and employed repeated measures to adjust for correlation between knees.
designActivated macrophages were present in the majority (76%) of knees. The quantity of knee-related macrophages was significantly associated with knee pain severity (R = 0.60, P < 0.0001) and radiographic knee OA severity including joint space narrowing (R = 0.68, P = 0.007), and osteophyte (R = 0.66, P = 0.001). Macrophages were also localized to joints commonly affected by OA including hand finger joints (12%), thumb bases (28%), shoulders (26%), great toes (18%) and ankles (12%). The presence of joint pain at fingers, wrists, ankles and great toes was significantly positively associated with presence of activated macrophages at these sites (P < 0.0001-0.04).
conclusionsThis study provides the first direct in vivo evidence for macrophage involvement in OA in a substantial proportion of human knees. The association of quantity of activated macrophages with radiographic knee OA severity and joint symptoms suggests that drugs targeting macrophages and macrophage-associated inflammatory pathways may have the potential to be both symptom and structure modifying.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.