Targeting Extracellular miR-21-TLR7 Signaling Provides Long-Lasting Analgesia in Osteoarthritis
| Autor: | Shinro Takai, Atsushi Sakai, Naoya Hoshikawa, Hidenori Suzuki |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Analgesic knee primary sensory neuron synovium Inflammation Osteoarthritis Pharmacology Article 03 medical and health sciences synovial fluid 0302 clinical medicine Toll-like receptor Drug Discovery medicine Extracellular Synovial fluid pain Receptor synovial tissue microRNA business.industry Chronic pain medicine.disease 030104 developmental biology 030220 oncology & carcinogenesis Joint pain Molecular Medicine medicine.symptom business |
| Zdroj: | Molecular Therapy. Nucleic Acids |
| ISSN: | 2162-2531 |
| DOI: | 10.1016/j.omtn.2019.11.011 |
| Popis: | Osteoarthritis (OA) is the most prevalent joint disorder associated with severe chronic pain. Although synovial inflammation is well correlated with pain severity, the molecular mechanism responsible for OA pain remains unclear. Here, we show that extracellular miR-21 released from synovial tissue mediates knee OA pain in surgical OA model rats. miR-21 was the most abundant among increased microRNAs (miRNAs) in the synovial tissue. miR-21 was released into extracellular space from the synovial tissue and increased in the synovial fluid. A single intra-articular injection of miR-21 inhibitor exerted long-term analgesia of knee OA pain, whereas miR-21 injection in naive rats caused knee joint pain. miR-21 mutant, which lacks the Toll-like receptor (TLR) binding motif, but not in the seed sequence, did not cause joint pain, suggesting a non-canonical mode of action different from translational repression. Consistent with this, the algesic effect of miR-21 was blocked by antagonizing TLR7. The TLR7 antagonist also exerted a long-lasting analgesic effect on knee OA pain. Therefore, extracellular miR-21 released from synovial tissue mediates knee OA pain through TLR7 activation in surgical OA model rats. Extracellular miRNA in the joint may be a plausible target for pain therapy, providing a novel analgesic strategy for OA. |
| Databáze: | OpenAIRE |
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