The (−1486T/C) promoter polymorphism of the TLR‐9 gene is associated with end‐stage knee osteoarthritis in a Chinese population

Su, Sui-Lung; Yang, Hsin Yi; Lee, Chian Her; Huang, Guo Shu; Salter, Donald; Lee, Herng Sheng

doi:10.1002/jor.21494

Cited by 25 publications

(28 citation statements)

References 21 publications

(23 reference statements)

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“…Accumulating studies reported that TLR-mediated responses were key inducers of pro-inflammatory cytokines, which directly or indirectly resulted in development of lymphatic pathology [56–59]. Studies reported that ligands for TLRs (including TLR-2, 3, 4, 9) induced or exacerbated arthritis in experimental models[52, 60]. NF-κB has been reported to regulate expressions of genes involved in OA [61].…”

Section: Discussionmentioning

confidence: 99%

Effects of TLR-2/NF-κB signaling pathway on the occurrence of degenerative knee osteoarthritis: an in vivo and in vitro study

Liu

Wang

et al. 2017

Oncotarget

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The study aims to explore the effects of TLR-2/NF-κB signaling pathway on the occurrence of degenerative knee osteoarthritis (OA). Degenerative knee OA and normal cartilage samples were collected from patients with degenerative knee OA receiving total knee arthroplasty and amputation. Expressions of TLR-2, NF-κB and MMP-13 were determined by qRT-PCR and immunochemistry. The chondrocytes were divided into control, IL-1β, IL-1β + anti-TLR-2 and IL-1β + PDTC groups. MTT assay and flow cytometry were performed to determine proliferation and apoptosis of the chondrocytes. Expressions of TLR-2, NF-κB and MMP-13 were measured by Western blotting. ELISA was conducted to detect the expressions of related inflammatory factors. The positive expressions of TLR, NF-κB and MMP13 were associated with body mass index (BMI), family history, exercise, and WOMAC scores of OA patients. Logistic regression analysis showed that OA influencing factors were TLR, NF-κB, MMP13, BMI, family history and exercise. Compared with normal chondrocytes, the expressions of TLR-2, NF-κB, MMP-13 and related inflammatory factors increased in degenerative knee OA. The chondrocytes in the IL-1β + anti-TLR-2 and IL-1β + PDTC groups showed lower apoptosis rates than those in the IL-1β group. Compared with the control group, increased expressions of TLR-2, NF-κB, phosphorylated-NF-κB (p-NF-κB), MMP-13, IL-1, IL-6 and TNF-α were found in the IL-1β group. In the IL-1β + anti-TLR-2 and IL-1β + PDTC groups, decreased expressions of NF-κB, p-NF-κB, MMP-13, IL-1, IL-6 and TNF-α were found compared with those in the IL-1β group. TLR-2/NF-κB signaling pathway contributes to the occurrence of degenerative knee OA.

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Section: Discussionmentioning

confidence: 99%

Effects of TLR-2/NF-κB signaling pathway on the occurrence of degenerative knee osteoarthritis: an in vivo and in vitro study

Liu

Wang

et al. 2017

Oncotarget

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“…A more recent study demonstrated that TLR2 and TLR4 signals are important in mediating catabolic responses and in increasing MMP-3 and MMP-13 production in murine cartilage explants (63). A recent genetic study in a Chinese population identified a TLR-9 polymorphism that is associated with the presence of radiographic knee OA (102). This report did not reveal an association with common TLR-2 or -4 polymorphisms, and how TLR-9 is linked to increased risk of OA is not yet clear.…”

Section: Pathways That May Promote Synovitis In Oamentioning

confidence: 99%

The role of synovitis in osteoarthritis pathogenesis

Scanzello

Goldring

2012

Bone

955

829

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Research into the pathophysiology of osteoarthritis (OA) has focused on cartilage and peri-articular bone, but there is increasing recognition that OA affects all of the joint tissues, including the synovium (SM). Under normal physiological conditions the synovial lining consists of a thin layer of cells with phenotypic features of macrophages and fibroblasts. These cells and the underlying vascularized connective tissue stroma form a complex structure that is an important source of synovial fluid (SF) components that are essential for normal cartilage and joint function. The histological changes observed in the SM in OA generally include features indicative of an inflammatory “synovitis”; specifically they encompass a range of abnormalities, such as synovial lining hyperplasia, infiltration of macrophages and lymphocytes, neoangiogenesis and fibrosis. The pattern of synovial reaction varies with disease duration and associated metabolic and structural changes in other joint tissues. Imaging modalities including Magnetic Resonance (MRI) and ultrasound (US) have proved useful in detecting and quantifying synovial abnormalities, but individual studies have varied in their methods of evaluation. Despite these differences, most studies have concluded that the presence of synovitis in OA is associated with more severe pain and joint dysfunction. In addition, synovitis may be predictive of faster rates of cartilage loss in certain patient populations. Recent studies have provided insights into the pathogenic mechanisms underlying the development of synovitis in OA. Available evidence suggests that the inflammatory process involves engagement of Toll-like receptors and activation of the complement cascade by degradation products of extracellular matrices of cartilage and other joint tissues. The ensuing synovial reaction can lead to synthesis and release of a wide variety of cytokines and chemokines. Some of these inflammatory mediators are detected in joint tissues and SF in OA and have catabolic effects on chondrocytes. These inflammatory mediators represent potential targets for therapeutic interventions designed to reduce both symptoms and structural joint damage in OA.

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“…Also, it seems that the TLR‐2 induced expression of collagenase contributes to the catabolism of cartilage affected by OA, suggesting that modulation of TLR expression or activation in chondrocytes can be a path that might block cartilage degradation . Results of recent studies show that some TLR polymorphisms are associated with predisposition to primary knee OA (KOA) in the Chinese population …”

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confidence: 99%

Interleukin‐17 and Toll‐like Receptor 10 genetic polymorphisms and susceptibility to large joint osteoarthritis

Vrgoč

Vrbanec

Eftedal

et al. 2017

Journal Orthopaedic Research

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Primary osteoarthritis (OA) is the most common type of a joint disease. It has a polygenic risk inheritance pattern and affects older people. The etiology of this disease is not fully understood. The aim of this study was to investigate the associations between polymorphisms in pro-inflammatory interleukin-17 (IL17A and IL17F) and anti-inflammatory Toll-like Receptor 10 (TLR10) genes with the risk for development of advanced stage hip and knee primary OA in the Croatian population. A total of 500 OA patients and 597 controls were genotyped for IL17A SNP (rs2275913), IL17F SNPs (rs763780 and rs1889570), and TLR10 (rs11096957) genes. The allelic and genotypic frequencies of IL17F SNP (rs763780) showed statistically significant differences in comparisons of controls with hip-but not knee-OA patients. The major allele (T) of rs763780 was associated with the lower risk for developing hip OA (p = 7.9 × 10 , OR = 0.45, 95%CI = 0.27-0.74), whereas the minor allele (C) was associated with susceptibility to hip OA (p = 7.9 × 10 , OR = 2.24, 95%CI = 1.35-3.72). The genotype T/T was associated with the protection to hip OA (p = 3.9 × 10 , OR = 0.41, 95%CI = 0.24-0.70), and, lastly, the genotype T/C was associated with the higher risk to acquiring hip OA (p = 2.6 × 10 , OR = 2.50, 95%CI = 1.47-4.25). TLR10 SNP rs11096957 was found significantly associated with predisposition to hip OA (p = 0.04, OR = 1.41, 95%CI = 1.02-1.94) but not knee OA. Our findings suggest that hip OA in Croatian population might have a different genetic risk regarding the IL17 and TLR10 gene locus than knee OA. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1684-1693, 2018.

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The (−1486T/C) promoter polymorphism of the TLR‐9 gene is associated with end‐stage knee osteoarthritis in a Chinese population

Cited by 25 publications

References 21 publications

Effects of TLR-2/NF-κB signaling pathway on the occurrence of degenerative knee osteoarthritis: an in vivo and in vitro study

Effects of TLR-2/NF-κB signaling pathway on the occurrence of degenerative knee osteoarthritis: an in vivo and in vitro study

The role of synovitis in osteoarthritis pathogenesis

Interleukin‐17 and Toll‐like Receptor 10 genetic polymorphisms and susceptibility to large joint osteoarthritis

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