ArticleArthritis & rheumatology (Hoboken, N.J.)2019
Attenuated Joint Tissue Damage Associated With Improved Synovial Lymphatic Function Following Treatment With Bortezomib in a Mouse Model of Experimental Posttraumatic Osteoarthritis.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04503941 (Ultrasound Examination of Inguinal Lymph Node and Knee Joint Slip Fluid Accumulation Was Used to Evaluate the Effect of Acupuncture on Knee Osteoarthritis), which is not on this map. Cited by 31 papers, 1 of them a synthesis that pooled it.
What it found
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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.
The trial behind it
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.
Ultrasound Examination of Inguinal Lymph Node and Knee Joint Slip Fluid Accumulation Was Used to Evaluate the Effect of Acupuncture on Knee Osteoarthritis
Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Phenotypic alteration of macrophages during osteoarthritis: a systematic review.Arthritis research & therapy · 2021Pooled it
- Vascular-lymphatic dual circulation in bone health and disease: Mechanistic coupling and translational therapeutics.Journal of orthopaedic translation · 2026Review
- Synergistic targeting of senolytic and senomorphic action with dual-engineered biomimetic macrophage nanovesicles for mitigating osteoarthritis.Bioactive materials · 2026Article
- Synovial fibroblasts modulate endothelial activation in an acute injury-on-a-chip model.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Crosstalk between bone and vasculature within bone.Fundamental research · 2026Review
- Evaluating Complexity in Orthopedic Tissue-on-a-Chip Systems.Advanced healthcare materials · 2026Review
- Flow cytometric identification of dynamic immune cell populations in a rat model of post-traumatic elbow contracture.Connective tissue research · 2026Article
- The role of the lymphatic system in musculoskeletal system health and disease: research progress and future directions.Bone research · 2026Review
- Crosstalk between lymphatic system and synovial inflammatory cells in osteoarthritis: molecular mechanisms and potential cell-based therapies.Journal of translational medicine · 2025Review
- Brain-cervical lymph node crosstalk contributes to brain injury induced by subarachnoid hemorrhage in mice.Nature communications · 2025Article
- Peripheral neuronal sensitization and neurovascular remodelling in osteoarthritis pain.Nature reviews. Rheumatology · 2025Review
- Lymphatic-immune interactions in the musculoskeletal system.Frontiers in immunology · 2025Review
- Reactive oxygen species (ROS)-mediated M1 macrophage-dependent nanomedicine remodels inflammatory microenvironment for osteoarthritis recession.Bioactive materials · 2024Article
- Lymphatic vessels: roles and potential therapeutic intervention in rheumatoid arthritis and osteoarthritis.Theranostics · 2024Review
- The role of vascular and lymphatic networks in bone and joint homeostasis and pathology.Frontiers in endocrinology · 2024Review
- Targeting Synovial Lymphatic Function as a Novel Therapeutic Intervention for Age-Related Osteoarthritis in Mice.Arthritis & rheumatology (Hoboken, N.J.) · 2023Article
- Osteoarthritis: a narrative review of molecular approaches to disease management.Arthritis research & therapy · 2023Review
- Rotator cuff healing is regulated by the lymphatic vasculature.Journal of orthopaedic translation · 2023Article
- Current understanding of osteoarthritis pathogenesis and relevant new approaches.Bone research · 2022Review
- Phenotype Diversity of Macrophages in Osteoarthritis: Implications for Development of Macrophage Modulating Therapies.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
objectiveTo investigate the roles of the synovial lymphatic system in the severity and progression of joint tissue damage and functional responses of synovial lymphatic endothelial cells (LECs) to macrophage subsets, and to evaluate the therapeutic potential of the proteasome inhibitor bortezomib (BTZ) in a mouse model of experimental posttraumatic osteoarthritis (OA).
methodsC57BL/6J wild-type mice received a meniscal ligamentous injury to induce posttraumatic knee OA. Lymphangiogenesis was blocked by a vascular endothelial growth factor receptor 3 (VEGFR-3) neutralizing antibody. Synovial lymphatic drainage was examined by near-infrared imaging. Joint damage was assessed by histology. RNA-sequencing and pathway analyses were applied to synovial LECs. Macrophage subsets in the mouse synovium were identified by flow cytometry and immunofluorescence staining. M1 and M2 macrophages were induced from mouse bone marrow cells, and their effects on LECs were examined in cocultures in the presence or absence of BTZ. The effects of BTZ on joint damage, LEC inflammation, and synovial lymphatic drainage were examined.
resultsInjection of a VEGFR-3 neutralizing antibody into the joints of mice with posttraumatic knee OA reduced synovial lymphatic drainage and accelerated joint tissue damage. Synovial LECs from the mouse OA joints had dysregulated inflammatory pathways and expressed high levels of inflammatory genes. The number of M1 macrophages was increased in the knee joints of mice with posttraumatic OA, thereby promoting the expression of inflammatory genes by LECs; this effect was blocked by BTZ. Treatment with BTZ decreased cartilage loss, reduced the expression of inflammatory genes by LECs, and improved lymphatic drainage in the knee joints of mice with posttraumatic OA.
conclusionExperimental posttraumatic knee OA is associated with decreased synovial lymphatic drainage, increased numbers of M1 macrophages, and enhanced inflammatory gene expression by LECs, all of which was improved by treatment with BTZ. Intraarticular administration of BTZ may represent a new therapy for the restoration of synovial lymphatic function in subjects with posttraumatic knee OA.
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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.