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dc.creatorPapathanasiou, I.en
dc.creatorKostopoulou, F.en
dc.creatorMalizos, K. N.en
dc.creatorTsezou, A.en
dc.date.accessioned2015-11-23T10:44:24Z
dc.date.available2015-11-23T10:44:24Z
dc.date.issued2015
dc.identifier10.1186/s13075-015-0674-6
dc.identifier.issn1478-6354
dc.identifier.urihttp://hdl.handle.net/11615/31938
dc.description.abstractIntroduction: 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/beta-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. Methods: 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 (Ch.P). Results: 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. Conclusions: 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.en
dc.source.uri<Go to ISI>://WOS:000357456400001
dc.subjectARTICULAR-CARTILAGEen
dc.subjectGENEen
dc.subjectTARGETen
dc.subjectOSTEOPOROSISen
dc.subjectANTIBODIESen
dc.subjectSTRENGTHen
dc.subjectMUTATIONen
dc.subjectCELLSen
dc.subjectWNTen
dc.subjectPTHen
dc.subjectRheumatologyen
dc.titleDNA 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 promoteren
dc.typejournalArticleen


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