ArticleArthritis research & therapy2021
Effects of adenovirus-mediated knockdown of IRAK4 on synovitis in the osteoarthritis rabbit model.
Article in Arthritis research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 15 citations in OpenAlex.
- Traditional Chinese medicine ointment combined with tuina therapy in treatment of pain and swelling after total knee arthroplasty.World journal of orthopedics · 2022Trial
- Research progress on exosomes from different sources in osteoarthritis and cartilage injury.Journal of orthopaedic surgery and research · 2025Review
- Reprogramming Macrophage Polarization, Depleting ROS by Astaxanthin and Thioketal-Containing Polymers Delivering Rapamycin for Osteoarthritis Treatment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Inflammatory Response Modulation by Low-Dose Anti-inflammatory Drugs Treatment in anCurrent medicinal chemistry · 2024Article
- IRAK4 inhibition: an effective strategy for immunomodulating peri-implant osseointegration via reciprocally-shifted polarization in the monocyte-macrophage lineage cells.BMC oral health · 2023Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundThe use of interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitor as a treatment for the inflammatory joint disease is a promising method. However, its underlying mechanism in osteoarthritis (OA) remains unclear. The purpose of this study is to look into the effects of adenovirus-mediated knockdown of IRAK4 on synovitis in the OA rabbit model.
methodsAd-shIRAK4 was injected two weeks after anterior cruciate ligament resection. Six weeks later, the rabbits were killed. The expression of IRAK4, TNFR-associated factor 6(TRAF6), TGF-activated kinase 1(TAK1), p-IKB kinase (p-IKK), p-nuclear factor kappa-B (p-NFκB), p38, and p-p38 in the synovial membrane was detected by western blot, qRT-PCR, and immunohistochemistry analysis. Immunohistochemistry was to detect the expression of IRAK4 proteins in articular cartilage. H&E staining was to assess the pathological changes of synovium and cartilage. The levels of interleukin (IL)-1β, tumor necrosis factor-α(TNF-α), and MMP-13 in the synovial fluid were measured by ELISA. X-ray and micro-computerized tomography (μCT) scans were used to assess knee joint conditions and microstructure of subchondral bone.
resultsIRAK4 expression levels in synovial tissues of the OA model group exhibited a significant upward trend. Ad-shIRAK4 significantly reduced IRAK4 mRNA expression in synovium tissues. Notably, Ad-shIRAK4 suppressed the Toll-like receptor/interleukin-1 receptor (TLR/IL-1R) signaling. In addition, in the Ad-shIRAK4 treatment group, we can see less inflammatory cell infiltration and reduced hyperplasia and angiogenesis. The levels of IL-1β, TNF-α, and MMP-13 in the synovial fluid in the OA model group were significantly higher than that in the control group, which were reduced by Ad-shIRAK4 treatment. Finally, Results of HE stains, immunohistochemistry, and μCT showed that Ad-shIRAK4 treatment has a protective effect on cartilage damage.
conclusionsIRAK4 is significantly upregulated in the synovium from the osteoarthritis rabbit model. In addition, Ad-shIRAK4 reduced the expression of IRAK4 and suppressed TLR/IL-1R signaling in the synovium from the osteoarthritis rabbit model. Ad-shIRAK4 could alleviate synovitis and cartilage degradation in the osteoarthritis rabbit model, and thus alleviate the symptoms of OA and prevent the progression of OA.
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