Activation of receptor for advanced glycation end products in osteoarthritis leads to increased stimulation of chondrocytes and synoviocytes

Steenvoorden, M.M.C.; Huizinga, Tom W J; Verzijl, Nicole; Bank, Ruud A.; Ronday, H.K.; Luning, Hilco A. F.; Lafeber, Floris P. J. G.; Toes, René E. M.; DeGroot, Jeroen

doi:10.1002/art.21523

Cited by 133 publications

(117 citation statements)

References 53 publications

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“…It has been well established that RAGE serves as an amplification factor in various inflammatory cellular dysfunctions and is associated with the development of diabetic vascular complications, neurodegenerative disorders, rheumatoid arthritis, and other inflammatory diseases (23,(51)(52)(53)(54). As a member of the Ig superfamily proteins, RAGE is capable of binding to multiple ligands thus mediating diverse functions.…”

Section: Discussionmentioning

confidence: 99%

Receptor for Advanced Glycation Endproducts Mediates Neutrophil Migration across Intestinal Epithelium

Zen

Chen

et al. 2007

The Journal of Immunology

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Receptor for advanced glycation endproducts (RAGE) is an Ig superfamily cell surface receptor that interacts with a diverse array of ligands associated with inflammatory responses. In this study, we provide evidence demonstrating that RAGE is involved in inflammatory responses in the intestines. We showed that RAGE is expressed in intestinal epithelial cells, primarily concentrated at the lateral membranes close to the apical cell junction complexes. Although RAGE expression was low in epithelium under normal conditions, this protein was up-regulated after treatment with the inflammatory cytokines IFN-γ and/or TNF-α. RAGE expression was also elevated in colon tissue samples from patients with inflammatory bowel diseases. Using in vitro transmigration assays, we found that RAGE mediates neutrophil (polymorphonuclear leukocytes (PMN)) adhesion to, and subsequent migration across, intestinal epithelial monolayers. This activity appears to be mediated by the binding of RAGE to the PMN-specific β2 integrin CD11b/CD18. Thus, these results provide a novel mechanism for the regulation of PMN transepithelial migration and may suggest a new therapeutic target for intestinal inflammation.

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Section: Discussionmentioning

confidence: 99%

Receptor for Advanced Glycation Endproducts Mediates Neutrophil Migration across Intestinal Epithelium

Zen

Chen

et al. 2007

The Journal of Immunology

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“…Compared with normal healthy cartilage, OA cartilage contains obvious accumulations of AGEs and shows upregulation of RAGE [27]. Studies have shown that inflammation-induced cartilage hypertrophy is induced by AGEs in OA.…”

Section: Discussionmentioning

confidence: 99%

Pioglitazone Inhibits Advanced Glycation End Product-Induced TNF-E and MMP-13 Expression via the Antagonism of NF-TB Activation in Chondrocytes

Chen

Ma²,

Zhang³

et al. 2014

Pharmacology

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Objective: Advanced glycation end products (AGEs) play a pivotal role in the initiation and progression of osteoarthritis (OA). Peroxisome proliferator-activated receptor-G (PPARG) has been shown to exhibit anti-inflammatory and anticatabolic properties and to be protective in animal models of OA. This study was aimed to investigate the possible protective effect of the PPARG agonist pioglitazone on AGE-induced chondrocyte damage. Methods: Cultured chondrocytes were stimulated with AGEs in the presence or absence of an antibody against the receptor for AGEs (anti-RAGE), an inhibitor of NF-TB (pyrrolidine dithiocarbamate) and pioglitazone. The RNA expression levels of TNF-E, matrix metalloproteinase (MMP)-13 and PPARG were detected by RT-PCR. The expression of nuclear p65 was determined by Western blot analysis. Results: Upregulation of TNF-E and MMP-13 as well as downregulation of PPARG were induced by AGEs in a time- and dose-dependent manner. The maximum effect was induced by 100 Vg/ml AGEs. This effect can be inhibited by anti-RAGE. Pioglitazone dose-dependently inhibited the expression of TNF-E and MMP-13 induced by AGEs, which was combined with the inhibition of nuclear p65 expression. Conclusion: The PPARG agonist pioglitazone modulates TNF-E and MMP-13 expression in cultured rabbit chondrocytes via NF-TB signaling. It indicates that pioglitazone may have therapeutic potential in OA. i 2014 S. Karger AG, Basel

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“…44 Activation of these receptors by cartilage damage as well as by proinflammatory cytokines contributes to the complex detrimental cascade of cartilage damage. As the disease progresses, these different cascades and events appear to function as positive feedback mechanisms with an avalanche-like effect on the destruction of the joints, the associated loss of function and with an increase in pain.…”

Section: Loss Of the Chondrocyte ' S Stable Phenotype -A Role For Dammentioning

confidence: 99%

Osteoarthritis, a disease bridging development and regeneration

Lories

Luyten²

2012

BoneKEy Reports

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The osteoarthritic diseases are common disorders characterized by progressive destruction of the articular cartilage in the joints, and associated with remodeling of the subchondral bone, synovitis and the formation of bone outgrowths at the joint margins, osteophytes. From the clinical perspective, osteoarthritis leads to joint pain and loss of function. Osteoarthritis is the leading cause of progressive disability. New data from genetic, translational and basic research have demonstrated that pathways with essential roles in joint and bone development also contribute to the postnatal homeostasis of the articular cartilage and are involved in osteoarthritis, making these potential therapeutic targets. Other systems of interest are the tissue-destructive enzymes that break down the extracellular matrix of the cartilage as well as mediators of inflammation that contribute to synovitis. However, the perspective of a durable treatment over years to decades highlights the need for a personalized medicine approach encompassing a global view on the disease and its management, thereby including nonpharmaceutical approaches such as physiotherapy and advanced surgical methods. Integration of novel strategies based on their efficacy and safety with the identification of individuals at risk and optimal individual rehabilitation management remains a major challenge for the medical community in particular, as the incidence of osteoarthritis is likely to further increase with the overall aging of the population.

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Activation of receptor for advanced glycation end products in osteoarthritis leads to increased stimulation of chondrocytes and synoviocytes

Cited by 133 publications

References 53 publications

Receptor for Advanced Glycation Endproducts Mediates Neutrophil Migration across Intestinal Epithelium

Receptor for Advanced Glycation Endproducts Mediates Neutrophil Migration across Intestinal Epithelium

Pioglitazone Inhibits Advanced Glycation End Product-Induced TNF-E and MMP-13 Expression via the Antagonism of NF-TB Activation in Chondrocytes

Osteoarthritis, a disease bridging development and regeneration

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