ArticleArthritis & rheumatology (Hoboken, N.J.)2015
Damage-associated molecular patterns generated in osteoarthritis directly excite murine nociceptive neurons through Toll-like receptor 4.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 104 citations in OpenAlex.
- Measuring Joint Pain Through Tibiofemoral Flexion: A Novel Approach to Assess Pain Behavior and Analgesic Profiles in Rats.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2026Article
- A neuroimmune axis linking S100A8/9 to itch sensitization in both bullous pemphigoid and atopic dermatitis.JID innovations : skin science from molecules to population health · 2026Article
- Neuroimmune interactions in arthritis: linking pain sensitisation and inflammation.Journal of bone and mineral metabolism · 2026Review
- Targeted knockdown of Piezo1 in synovial macrophages attenuates osteoarthritis development.Journal of orthopaedic translation · 2026Article
- Chemokine CCL2 Mediates Neuroglial Crosstalk and Drives Chronic Pain Pathogenesis.Neuroscience bulletin · 2025Review
- A Review of Rodent Behavior, Mobility, and Pain Modifications in Response to Destabilization of the Medial Meniscus Injury.Biomedicines · 2025Review
- Multi-omics analysis of small extracellular vesicles in osteoarthritis: bridging the gap between molecular insights and clinical applications.Burns & trauma · 2025Review
- Activation of TLR4/CCL2 in Intact Neurons Drives Radicular Injury-Induced Global Nerve Trunk Hypersensitivity in Radiculopathy Preclinical Models.Journal of pain research · 2025Article
- Acute systemic macrophage depletion in osteoarthritic mice alleviates pain-related behaviors and does not affect joint damage.Arthritis research & therapy · 2024Article
- Neural and immune roles in osteoarthritis pain: Mechanisms and intervention strategies.Journal of orthopaedic translation · 2024Review
- Acute systemic macrophage depletion in osteoarthritic mice alleviates pain-related behaviors and does not affect joint damage.bioRxiv : the preprint server for biology · 2024Article
- Potential therapeutic strategies for osteoarthritis via CRISPR/Cas9 mediated gene editing.Reviews in endocrine & metabolic disorders · 2024Review
- TLR4 antagonism provides short-term but not long-term clinical benefit in a full-depth cartilage defect mouse model.Connective tissue research · 2024Article
- Engineering a multicompartment in vitro model for dorsal root ganglia phenotypic assessment.Journal of biomedical materials research. Part B, Applied biomaterials · 2023Article
- The potential role of synovial cells in the progression and treatment of osteoarthritis.Exploration (Beijing, China) · 2023Review
- Neuroimmune Mechanisms Underlying Post-acute Sequelae of SARS-CoV-2 (PASC) Pain, Predictions from a Ligand-Receptor Interactome.Current rheumatology reports · 2023Review
- Crisaborole Inhibits Itch and Pain by Preventing Neutrophil Infiltration in a Mouse Model of Atopic Dermatitis.Acta dermato-venereologica · 2023Article
- Pyruvate Dehydrogenase Kinase 1 inhibition mediated oxidative phosphorylation enhancement in cartilage promotes osteoarthritis progression.BMC musculoskeletal disorders · 2023Article
- Role of circular RNAs in osteoarthritis: update on pathogenesis and therapeutics.Molecular genetics and genomics : MGG · 2023Review
- Notch signaling is activated in knee-innervating dorsal root ganglia in experimental models of osteoarthritis joint pain.Arthritis research & therapy · 2023Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveTo determine whether selected damage-associated molecular patterns (DAMPs) present in the osteoarthritic (OA) joints of mice excite nociceptors through Toll-like receptor 4 (TLR-4).
methodsThe ability of S100A8 and α2 -macroglobulin to excite nociceptors was determined by measuring the release of monocyte chemoattractant protein 1 (MCP-1) by cultured dorsal root ganglion (DRG) cells as well as by measuring the intracellular calcium concentration ([Ca(2+) ]i ) in cultured DRG neurons from naive mice or from mice that had undergone surgical destabilization of the medial meniscus (DMM) 8 weeks previously. The role of TLR-4 was assessed using TLR-4(-/-) cells or a TLR-4 inhibitor. The [Ca(2+) ]i in neurons within ex vivo intact DRGs was measured in samples from Pirt-GCaMP3 mice. Neuronal expression of the Tlr4 gene was determined by in situ hybridization. DMM surgery was performed in wild-type and TLR-4(-/-) mice; mechanical allodynia was monitored, and joint damage was assessed histologically after 16 weeks.
resultsDRG neurons from both naive and DMM mice expressed Tlr4. Both S100A8 and α2 -macroglobulin stimulated release of the proalgesic chemokine MCP-1 in DRG cultures, and the neurons rapidly responded to S100A8 and α2 -macroglobulin with increased [Ca(2+) ]i . Blocking TLR-4 inhibited these effects. Neurons within intact DRGs responded to the TLR-4 agonist lipopolysaccharide. In both of the calcium-imaging assays, it was primarily the nociceptor population of neurons that responded to TLR-4 ligands. TLR-4(-/-) mice were not protected from mechanical allodynia or from joint damage associated with DMM.
conclusionOur experiments suggest a role of TLR-4 signaling in the excitation of nociceptors by selected DAMPs. Further research is needed to delineate the importance of this pathway in relation to OA pain.
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