ArticleJBMR plus2019
TLR4 Promotes and DAP12 Limits Obesity-Induced Osteoarthritis in Aged Female Mice.
Article in JBMR plus, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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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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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- KARAP deficiency alleviates intestinal mucosal barrier dysfunction by regulating mitochondrial homeostasis in macrophages.Precision clinical medicine · 2026Article
- miR-655-3p is a highly accurate diagnostic biomarker for primary osteoarthritis and alleviates joint inflammation by targeting TLR4.Acta orthopaedica et traumatologica turcica · 2026Article
- Review
- From pathogenesis to therapy: extracellular vesicles in osteoarthritis.Frontiers in bioengineering and biotechnology · 2026Review
- Article
- Microbial Symphony: Exploring the Role of the Gut in Osteoarthritis-Related Pain. A Narrative Review.Pain and therapy · 2024Review
- Toll-like receptor 4 (TLR4): new insight immune and aging.Immunity & ageing : I & A · 2023Review
- The burden of osteoarthritis due to high Body Mass Index in Iran from 1990 to 2019.Scientific reports · 2023Article
- NOS inhibition reverses TLR2-induced chondrocyte dysfunction and attenuates age-related osteoarthritis.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Targeting the Inflammatory Hallmarks of Obesity-Associated Osteoarthritis: Towards Nutraceutical-Oriented Preventive and Complementary Therapeutic Strategies Based on n-3 Polyunsaturated Fatty Acids.International journal of molecular sciences · 2023Review
- The immune role of the intestinal microbiome in knee osteoarthritis: a review of the possible mechanisms and therapies.Frontiers in immunology · 2023Review
- Effects of synovial macrophages in osteoarthritis.Frontiers in immunology · 2023Review
- Obesity, Inflammation, and Immune System in Osteoarthritis.Frontiers in immunology · 2022Review
- Lipopolysaccharide Binding Protein and CD14, Cofactors of Toll-like Receptors, Are Essential for Low-Grade Inflammation-Induced Exacerbation of Cartilage Damage in Mouse Models of Posttraumatic Osteoarthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2021Article
- Leptin Induced TLR4 Expression via the JAK2-STAT3 Pathway in Obesity-Related Osteoarthritis.Oxidative medicine and cellular longevity · 2021Article
- Monocytes, Macrophages, and Their Potential Niches in Synovial Joints - Therapeutic Targets in Post-Traumatic Osteoarthritis?Frontiers in immunology · 2021Review
- TAP2, a peptide antagonist of Toll-like receptor 4, attenuates pain and cartilage degradation in a monoiodoacetate-induced arthritis rat model.Scientific reports · 2020Article
- Role of TLR2 and TLR4 in regulation of articular chondrocyte homeostasis.Osteoarthritis and cartilage · 2020Article
- Network Pharmacology Approach to Uncover the Mechanism Governing the Effect of Radix Achyranthis Bidentatae on Osteoarthritis.BMC complementary medicine and therapies · 2020Article
- An emerging role for Toll-like receptors at the neuroimmune interface in osteoarthritis.Seminars in immunopathology · 2019Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Aging and female sex are the strongest risk factors for nontraumatic osteoarthritis (OA); whereas obesity is a modifiable risk factor accelerating OA. Prior studies indicate that the innate immune receptor toll-like receptor 4 (TLR4) mediates obesity-induced metabolic inflammation and cartilage catabolism via recognition of damage-associated molecular patterns and is increased with aging in OA joints. TLR4 responses are limited by innate immunoreceptor adapter protein DNAX-activating protein of 12kDA (DAP12). We undertook this study to test the hypothesis that TLR4 promotes, whereas DAP12 limits, obesity-accelerated OA in aged female mice. We fed 13- to 15-month-old female WT, TLR4 KO, and DAP12 KO mice a high-fat diet (HFD) or a control diet for 12 weeks, and changes in body composition, glucose tolerance, serum cytokines, and insulin levels were compared. Knee OA was evaluated by histopathology and μCT. Infrapatellar fat pads (IFPs) were analyzed by histomorphometry and F4/80+ crown-like structures were quantified. IFPs and synovium gene expression were analyzed using a targeted insulin resistance and inflammation array. All HFD-treated mice became obese, but only WT and TLR4 KO mice developed glucose intolerance. HFD induced cartilage catabolism in WT and DAP12 KO female mice, but not in TLR4 KO mice. Gene-expression analysis of IFPs and synovium showed significant differences in insulin signaling, adipokines, and inflammation between genotypes and diets. Unlike young mice, systemic inflammation was not induced by HFD in the older female mice independent of genotype. Our findings support the conclusion that TLR4 promotes and DAP12 limits HFD-induced cartilage catabolism in middle-aged female mice.
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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.