ArticleAnnals of the rheumatic diseases2016
Netrin-1 is highly expressed and required in inflammatory infiltrates in wear particle-induced osteolysis.
Article in Annals of the rheumatic diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 43 citations in OpenAlex.
- The Flavonoid Kaempferol Mitigates Periprosthetic Osteolysis by Regulating the NLRP3 Inflammasome and Balancing Bone Metabolism.Journal of cellular and molecular medicine · 2025Article
- RhoA GAP Myo9b regulates β2-integrin activity and neutrophil recruitment during murine acute kidney injury.Blood · 2025Article
- Integrative genomic analysis identifies novel causal genes of Hodgkin's and non-Hodgkin's lymphoma.Discover oncology · 2025Article
- The effect of barium titanate-coated titanium alloy scaffolds on bone regeneration in osteonecrosis of the femoral head models: a comprehensive analysis based onFrontiers in bioengineering and biotechnology · 2025Article
- Targeting Unc5b in macrophages drives atherosclerosis regression and pro-resolving immune cell function.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- DNA Methylation-Mediated GPX4 Transcriptional Repression and Osteoblast Ferroptosis Promote Titanium Particle-Induced Osteolysis.Research (Washington, D.C.) · 2024Article
- Inhibition of EGFR Pathway Suppresses M1 Macrophage Polarization and Osteoclastogenesis, Mitigating Titanium Particle-Induced Bone Resorption.Journal of inflammation research · 2024Article
- Therapeutic effects of MSCs, genetically modified MSCs, and NFĸB-inhibitor on chronic inflammatory osteolysis in aged mice.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2023Article
- Netrin-1 Secreted by Human Osteoarthritic Articular Chondrocytes Promotes AngiogenesisCartilage · 2022Article
- Spinal TRPA1 Contributes to the Mechanical Hypersensitivity Effect Induced by Netrin-1.International journal of molecular sciences · 2022Article
- Netrin-1: A Modulator of Macrophage Driven Acute and Chronic Inflammation.International journal of molecular sciences · 2021Review
- The expression of Netrin-1 in the MIA-induced osteoarthritic temporomandibular joint in mice.Scientific reports · 2021Article
- Axon Guidance Molecules Guiding Neuroinflammation.Experimental neurobiology · 2019Review
- Lack of Myosin X Enhances Osteoclastogenesis and Increases Cell Surface Unc5b in Osteoclast-Lineage Cells.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2019Article
- Puerarin Exerts Protective Effects on Wear Particle-Induced Inflammatory Osteolysis.Frontiers in pharmacology · 2019Article
- Macrophage-derived netrin-1 promotes abdominal aortic aneurysm formation by activating MMP3 in vascular smooth muscle cells.Nature communications · 2018Article
- Netrins & Semaphorins: Novel regulators of the immune response.Biochimica et biophysica acta. Molecular basis of disease · 2017Review
- Titanium particle-induced osteogenic inhibition and bone destruction are mediated by the GSK-3β/β-catenin signal pathway.Cell death & disease · 2017Article
- Lentiviral-Mediated Netrin-1 Overexpression Improves Motor and Sensory Functions in SCT Rats Associated with SYP and GAP-43 Expressions.Molecular neurobiology · 2017Article
- Netrin-1 and its receptor Unc5b are novel targets for the treatment of inflammatory arthritis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveNetrin-1 is a chemorepulsant and matrix protein expressed during and required for osteoclast differentiation, which also plays a role in inflammation by preventing macrophage egress. Because wear particle-induced osteolysis requires osteoclast-mediated destruction of bone, we hypothesised that blockade of Netrin-1 or Unc5b, a receptor for Netrin-1, may diminish this pathological condition.
methodsC57BL/6 mice, 6-8 weeks old, had 3 mg of ultrahigh-molecular-weight polyethylene particles implanted over the calvaria and then received 10 µg of monoclonal antibodies for Netrin-1 or its receptors, Unc5b and deleted in colon cancer (DCC), injected intraperitoneally on a weekly basis. After 2 weeks, micro-computed tomography and histology analysis were performed. Netrin-1 expression was analysed in human tissue obtained following primary prosthesis implantation or after prosthesis revision for peri-implant osteolysis and aseptic implant loosening.
resultsWeekly injection of anti-Netrin-1 or anti-Unc5b-antibodies significantly reduced particle-induced bone pitting in calvaria exposed to wear particles (46±4% and 49±3% of control bone pitting, respectively, p<0.001) but anti-DCC antibody did not affect inflammatory osteolysis (80±7% of control bone pitting, p=ns). Anti-Netrin-1 or anti-Unc5b, but not anti-DCC, antibody treatment markedly reduced the inflammatory infiltrate and the number of tartrate resistance acid phosphatase (TRAP)-positive osteoclasts (7±1, 4±1 and 14±1 cells/high power field (hpf), respectively, vs 12±1 cells/hpf for control, p<0.001), with no significant changes in alkaline phosphatase-positive osteoblasts on bone-forming surfaces in any antibody-treated group. Netrin-1 immunostaining colocalised with CD68 staining for macrophages. The peri-implant tissues of patients undergoing prosthesis revision surgery showed an increase in Netrin-1 expression, whereas there was little Netrin-1 expression in soft tissues removed at the time of primary joint replacement.
conclusionsThese results demonstrate a unique role for Netrin-1 in osteoclast biology and inflammation and may be a novel target for prevention/treatment of inflammatory osteolysis.
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