Expression and regulation of Toll-like receptor 2 by IL-1β and fibronectin fragments in human articular chondrocytes

Su, Sui-Lung; Tsai, Chia‐Kuang; Lee, C. H.; Salter, Donald; Lee, Herng Sheng

doi:10.1016/j.joca.2005.04.017

Cited by 88 publications

(98 citation statements)

References 55 publications

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“…In contrast to hitherto-inconsistent observations regarding the presence of some of the TLRs in articular chondrocytes (25)(26)(27), we found clear evidence of the expression of TLRs 1-9 in human articular chondrocytes on the mRNA level. Interestingly, TLR-7 was only demonstrable in chondrocytes derived from patients younger than age 35 years, suggesting that a patient's age may influence TLR expression, which is consistent with previous observations of the effects of aging in cartilage biology, particularly with regard to matrix synthesis and cell numbers, each of which shows a dramatic decrease in patients around age 30 years (24,(46)(47)(48)(49)(50).…”

Section: Discussioncontrasting

confidence: 99%

“…The expression of some members of the TLR family has been examined in previous studies, although the existing data are contradictory (25)(26)(27). To determine the expression profiles of TLRs 1-9 in postnatal articular chondrocytes, RT-PCR analysis of total RNA in chondrocytes obtained from human articular cartilage was performed; total RNA derived from PBMCs served as a positive control.…”

Section: Resultsmentioning

confidence: 99%

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Toll‐like receptors and chondrocytes: The lipopolysaccharide‐induced decrease in cartilage matrix synthesis is dependent on the presence of toll‐like receptor 4 and antagonized by bone morphogenetic protein 7

Bobacz

Sunk

Hofstaetter

et al. 2007

Arthritis & Rheumatism

106

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Conclusion.These data demonstrate the presence of TLRs in human articular cartilage. The suppressive effects of LPS on cartilage biosynthetic activity are dependent on the presence of TLR-4, are governed, at least in part, by an up-regulation of IL-1␤, and are mediated by p38 kinase. These in vitro data indicate an anti-anabolic effect of TLR-4 in articular chondrocytes that may hamper cartilage repair in various joint diseases.

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Section: Discussioncontrasting

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Toll‐like receptors and chondrocytes: The lipopolysaccharide‐induced decrease in cartilage matrix synthesis is dependent on the presence of toll‐like receptor 4 and antagonized by bone morphogenetic protein 7

Bobacz

Sunk

Hofstaetter

et al. 2007

Arthritis & Rheumatism

106

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“…Human articular chondrocytes were shown to express a variety of TLRs in vivo. 6 In cartilage degeneration TLR2 and TLR4 reappear on the chondrocyte membrane, 2,6 both underlining the involvement of an inflammatory component and concurrently reminiscing TLR expression during embryological developmental stages. In primary OA chondrocytes in culture this upregulation of TLR2 (and TLR4, although not significantly) was induced by the proinflammatory cytokines IL-1b and TNFa.…”

Section: Discussionmentioning

confidence: 99%

“…3,4 Furthermore they play a role in noninfected rheumatoid arthritis (RA) and in the primarily degenerative joint disease osteoarthritis (OA). [1][2][3]5,6 In degenerative tendinopathies the balance between matrix synthesis and degradation is disturbed, and increased MMP activity as well as an increased percentage of degraded collagen are found. [7][8][9] An increase in NO synthase expression was found in a supraspinatus tendon overuse model 10 and an increase in COX2, a key regulator of prostaglandin synthesis was found in patellar tendinopathy.…”

mentioning

confidence: 99%

“…11 These catabolic activities can be influenced by TLR signalling, as shown in experiments with chondrocytes. 2,6 Furthermore, increased expression of subunit B of the endogenous TLR ligand fibronectin has been found in Achilles tendinopathy. 12 The presence of other endogenous TLR ligands known so far (heat-shock proteins, necrotic cells, hyaluronan) in tendinopathy is very likely considering the nature of the pathology.…”

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confidence: 99%

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Tendon degeneration is not mediated by regulation of Toll‐like receptors 2 and 4 in human tenocytes

Mos

Joosten

Oppers‐Walgreen

et al. 2009

Journal Orthopaedic Research

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We hypothesized that expression of Toll-like receptors (TLRs) 2 and 4 by tenocytes is involved in the catabolic processes of tendon degeneration. We investigated TLR2 and TLR4 expression by tenocytes in healthy and tendinotic Achilles tendons. We also investigated whether TLR2 and TLR4 could be upregulated in tendon explants using proinflammatory cytokines interleukin (IL)-1b and tumor necrosis factor alphpa (TNFa). Peroperatively harvested healthy (n ¼ 5) and tendinotic (n ¼ 13) Achilles tendon samples were examined by real-time RT-PCR and immunohistochemical staining for TLR2 and TLR4. In addition, the catabolic process in tendinopathy was analyzed by real-time RT-PCR for matrix metalloproteinases MMP1, MMP3, MMP9, and MMP13. Furthermore, healthy tendon explants were cultured in the presence of 20 ng/ml IL-1b (n ¼ 10) or 10 ng/mL TNFa (n ¼ 8) for 4, 24, 48, and 72 h before analysis of TLR and MMP expression levels. Although mRNA levels for both TLR2 and TLR4 were detected in healthy and tendinotic Achilles tendons, we could not confirm expression of these receptors by immunohistochemical staining in either healthy or tendinotic tendon samples. Both receptors did not show significant transcriptional regulation in tendinopathy, although MMP3 was downregulated and MMP9 was upregulated in tendinopathy. In tendon explant cultures TLR2 mRNA was upregulated by TNFa (p < 0.05) and IL-1b (not significant). TLR4 gene expression was not altered by addition of IL-1b or TNFa. Tendon tissue can be stimulated to increase TLR2 gene expression by addition of catabolic factors TNFa or IL-1b. However, the catabolic processes in Achilles tendinopathy cannot be attributed to regulation of TLR2 and TLR4 by tenocytes. Toll-like receptors (TLRs) are phylogenetically conserved transmembrane receptors belonging to the family of pattern-recognition receptors (PRR). In humans, 11 TLR homologs have been identified thus far, expressed by numerous cell types like monocytes and dendritic cells, 1 and for example by chondrocytes. 2 TLRs detect microbial components, but TLR2 and TLR4 also recognize endogenous ligands like heat-shock proteins, necrotic cells, hyaluronan, and fibronectin. 1 Ligand recognition elicits an immune response with upregulation and activation of proinflammatory cytokines and matrix-metalloproteinases (MMPs). 2 Hence, via endogenous ligand recognition the TLR-mediated catabolic signalling pathways can directly contribute to degradative tissue reactions even in the absence of microbial components. TLRs are implicated in inflammatory and autoimmune diseases, but also in disorders like atherosclerosis and cancer. 3,4 Furthermore they play a role in noninfected rheumatoid arthritis (RA) and in the primarily degenerative joint disease osteoarthritis (OA). [1][2][3]5,6 In degenerative tendinopathies the balance between matrix synthesis and degradation is disturbed, and increased MMP activity as well as an increased percentage of degraded collagen are found. 7-9 An increase in NO synthase expression was found in a sup...

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The catabolic pathway mediated by Toll‐like receptors in human osteoarthritic chondrocytes

Kim

Cho²,

Choi

et al. 2006

Arthritis & Rheumatism

249

220

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Expression and regulation of Toll-like receptor 2 by IL-1β and fibronectin fragments in human articular chondrocytes

Cited by 88 publications

References 55 publications

Toll‐like receptors and chondrocytes: The lipopolysaccharide‐induced decrease in cartilage matrix synthesis is dependent on the presence of toll‐like receptor 4 and antagonized by bone morphogenetic protein 7

Toll‐like receptors and chondrocytes: The lipopolysaccharide‐induced decrease in cartilage matrix synthesis is dependent on the presence of toll‐like receptor 4 and antagonized by bone morphogenetic protein 7

Tendon degeneration is not mediated by regulation of Toll‐like receptors 2 and 4 in human tenocytes

The catabolic pathway mediated by Toll‐like receptors in human osteoarthritic chondrocytes

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