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DNA methylation regulates sclerostin (SOST) expression in osteoarthritic chondrocytes by bone morphogenetic protein 2 (BMP-2) induced changes in Smads binding affinity to the CpG region of SOST…

Overview of attention for article published in Arthritis Research & Therapy, June 2015
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Title
DNA methylation regulates sclerostin (SOST) expression in osteoarthritic chondrocytes by bone morphogenetic protein 2 (BMP-2) induced changes in Smads binding affinity to the CpG region of SOST promoter
Published in
Arthritis Research & Therapy, June 2015
DOI 10.1186/s13075-015-0674-6
Pubmed ID
Authors

Ioanna Papathanasiou, Fotini Kostopoulou, Konstantinos N. Malizos, Aspasia Tsezou

Abstract

Sclerostin (SOST), a soluble antagonist of Wnt signaling, is expressed in chondrocytes and contributes to chondrocytes' hypertrophic differentiation; however its role in osteoarthritis (OA) pathogenesis is not well known. Based on our previous findings on the interaction between Wnt/β-catenin pathway and BMP-2 in OA, we aimed to investigate the role of DNA methylation and BMP-2 on SOST's expression in OA chondrocytes. SOST mRNA and protein expression levels were investigated using real-time polymerase chain reaction (PCR) and Western blot, respectively. The methylation status of SOST promoter was analysed using methylation-specific PCR (MSP), quantitative methylation-specific PCR (qMSP) and bisulfite sequencing analysis. The effect of BMP-2 and 5'-Aza-2-deoxycytidine (5-AzadC) on SOST's expression levels were investigated and Smad1/5/8 binding to SOST promoter was assessed by Chromatin Immunoprecipitation (ChΙP). We observed that SOST's expression was upregulated in OA chondrocytes compared to normal. Moreover, we found that the CpG region of SOST promoter was hypomethylated in OA chondrocytes and 5-AzadC treatment in normal chondrocytes resulted in decreased SOST methylation, whereas its expression was upregulated. BMP-2 treatment in 5-AzadC-treated normal chondrocytes resulted in SOST upregulation, which was mediated through Smad 1/5/8 binding on the CpG region of SOST promoter. We report novel findings that DNA methylation regulates SOST's expression in OA, by changing Smad 1/5/8 binding affinity to SOST promoter, providing evidence that changes in DNA methylation pattern could underlie changes in genes' expression observed in OA.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 60 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 2%
Unknown 59 98%

Demographic breakdown

Readers by professional status Count As %
Researcher 10 17%
Student > Ph. D. Student 9 15%
Professor 6 10%
Student > Doctoral Student 5 8%
Student > Bachelor 4 7%
Other 9 15%
Unknown 17 28%
Readers by discipline Count As %
Medicine and Dentistry 20 33%
Biochemistry, Genetics and Molecular Biology 12 20%
Agricultural and Biological Sciences 5 8%
Pharmacology, Toxicology and Pharmaceutical Science 1 2%
Veterinary Science and Veterinary Medicine 1 2%
Other 3 5%
Unknown 18 30%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 14 June 2015.
All research outputs
#22,759,802
of 25,374,917 outputs
Outputs from Arthritis Research & Therapy
#3,132
of 3,381 outputs
Outputs of similar age
#237,657
of 278,767 outputs
Outputs of similar age from Arthritis Research & Therapy
#56
of 61 outputs
Altmetric has tracked 25,374,917 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,381 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.2. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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We're also able to compare this research output to 61 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.