Expression of ADAMTS-4 by chondrocytes in the surface zone of human osteoarthritic cartilage is regulated by epigenetic DNA de-methylation

Cheung, Kelvin; Hashimoto, Kazuhito; Yamada, Norikazu; Roach, Helmtrud I.

doi:10.1007/s00296-008-0744-z

Cited by 107 publications

(77 citation statements)

References 23 publications

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“…The active forms of ADAMTS-4 were increased in synovial fluid samples from patients with active Lyme arthritis (Behera et al, 2006). Expression of ADAMTS-4 in the surface zone of human osteoarthritic cartilage is regulated by epigenetic DNA demethylation (Cheung et al, 2009). Suppression of ADAMTS-4 and ADAMTS-5, individually or in combination, attenuated the degradation of aggrecan in cytokine-stimulated normal cartilage (Song et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Increased serum ADAMTS-4 in knee osteoarthritis: a potential indicator for the diagnosis of osteoarthritis in early stages

Li¹,

Du²,

Wang³

et al. 2014

Genet. Mol. Res.

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ABSTRACT. We compared serum levels of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, ADAMTS-5, matrix metalloproteinase (MMP)-1, and MMP-3 in patients with different stages of knee osteoarthritis (OA), and investigated the clinical significance of diagnosing OA in early stages. OA patients were divided into 2 groups: early OA group (44 cases), intermediate and advanced OA group (26 cases). The healthy control group included 30 samples. ADAMTS-4, ADAMTS-5, MMP-1, and MMP-3 levels in the serum were tested using an enzyme-linked immunosorbent assay. A protein-protein interaction network was constructed by seeding the significantly expressed marker, followed by Gene Ontology enrichment analyses using Database for Annotation, Visualization and Integrated Discovery. ADAMTS-4 levels were significantly higher in patients at early stages of OA compared to intermediate or advanced OA and healthy controls. ADAMTS-5, MMP-1, and MMP-3 levels in intermediate and advanced-stage OA patients were significantly higher than those in early-stage OA patients and healthy controls. The proteinprotein interaction network showed that ADAMTS-4 participates in

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Section: Discussionmentioning

confidence: 99%

Increased serum ADAMTS-4 in knee osteoarthritis: a potential indicator for the diagnosis of osteoarthritis in early stages

Li¹,

Du²,

Wang³

et al. 2014

Genet. Mol. Res.

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“…The epigenetic state of the Sox9 promoter has been described to change during the process of OA [21]. In the same way, promoters for several metalloproteinases have been described as less methylated in OA-derived samples [22][23][24]. However, other studies have yielded results that could not demonstrate significant gene methylation in the aggrecan promoter of aged and OA chondrocytes [25].…”

Section: Discussionmentioning

confidence: 67%

The role of Alk-1 and Alk-5 in the mechanosensing of chondrocytes

Sanz-Ramos

Dotor²,

Izal-Azcárate

2014

Cellular and Molecular Biology Letters

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Abbreviations used: Alk-1 -activin receptor-like kinase 1; Alk-5 -activin receptor-like kinase 5; FGFR3 -fibroblast growth factor receptor 3; FA -focal adhesions; MSCsmesenchymal stem cells; OA -osteoarthritis; TGFβ -transforming growth factor β; Col2 -type II collagen; Col1 -type I collagen; Col10 -type X collagen Abstract: We aim to demonstrate the role of Alk receptors in the response of hydrogel expansion. Chondrocytes from rat knees were cultured onto plastic and hydrogel surfaces. Alk-1 and Alk-5 were overexpressed or silenced and the effects on cells during expansion were tested and confirmed using peptide inhibitors for TGFβ. Overexpression of Alk-5 and silencing of Alk-1 led to a loss of the chondrocyte phenotype, proving that they are key regulators of chondrocyte mechanosensing. An analysis of the gene expression profile during the expansion of these modified cartilage cells in plastic showed a better maintenance of the chondrocyte phenotype, at least during the first passages. These passages were also assayed in a mouse model of intramuscular chondrogenesis. Our findings indicate that these two receptors are important mediators in the response of chondrocytes to changes in the mechanical environment, making them suitable targets for modulating chondrogenesis. Inhibition of TGFβ could also be effective in improving chondrocyte activity in aged or expanded cells that overexpress Alk-1.

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“…OA is characterized by progressive structural changes in the articular cartilage, accompanied by new bone formation, changes in the subchondral bone and a low-grade synovitis [7]. The disease eventually leads to the loss of joint function, pain and immobility [8]. Despite high frequency of the disease, its cause is still not completely elucidated.…”

Section: Osteoarthritismentioning

confidence: 99%

MicroRNAs: Important Epigenetic Regulators in Osteoarthritis

Trzeciak¹,

Czarny-Ratajczak²

2015

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Multiple mechanisms are implicated in the development of primary osteoarthritis (OA), in which genetic and epigenetic factors appear to interact with environmental factors and age to initiate the disease and stimulate its progression. Changes in expression of microRNAs (miRs) contribute to development of osteoarthritis. Numerous miRs are involved in cartilage development, homeostasis and degradation through targeting genes expressed in this tissue. An important regulator of gene expression in human cartilage is miR-140, which directly targets a gene coding aggrecanase ADAMTS-5, that cleaves aggrecan in cartilage. This miR is considered a biological marker for cartilage and its level significantly decreases in OA cartilage. On the other hand, increased expression of miR-146a in early OA inhibits two other cartilage-degrading enzymes: MMP13 and ADAMTS4, and may provide a useful tool in developing treatments for OA. The COL2A1 gene, encoding collagen type II, which is the most abundant structural protein of the cartilage, is silenced by miR-34a and activated by miR-675. Every year, new targets of cartilage miRs are validated experimentally and this opens new possibilities for new therapies that control joint destruction and stimulate cartilage repair. At the same time development of next-generation sequencing technologies allows to identify new miRs involved in cartilage biology.

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Expression of ADAMTS-4 by chondrocytes in the surface zone of human osteoarthritic cartilage is regulated by epigenetic DNA de-methylation

Cited by 107 publications

References 23 publications

Increased serum ADAMTS-4 in knee osteoarthritis: a potential indicator for the diagnosis of osteoarthritis in early stages

Increased serum ADAMTS-4 in knee osteoarthritis: a potential indicator for the diagnosis of osteoarthritis in early stages

The role of Alk-1 and Alk-5 in the mechanosensing of chondrocytes

MicroRNAs: Important Epigenetic Regulators in Osteoarthritis

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