RT Journal Article
SR Electronic
T1 <em>SMAD3</em> Is Upregulated in Human Osteoarthritic Cartilage Independent of the Promoter DNA Methylation
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP 388
OP 394
DO 10.3899/jrheum.150609
VO 43
IS 2
A1 Erfan Aref-Eshghi
A1 Ming Liu
A1 Seyd Babak Razavi-Lopez
A1 Kensuke Hirasawa
A1 Patricia E. Harper
A1 Glynn Martin
A1 Andrew Furey
A1 Roger Green
A1 Guang Sun
A1 Proton Rahman
A1 Guangju Zhai
YR 2016
UL http://www.jrheum.org/content/43/2/388.abstract
AB Objective. To compare SMAD3 gene expression between human osteoarthritic and healthy cartilage and to examine whether expression is regulated by the promoter DNA methylation of the gene.Methods. Human cartilage samples were collected from patients undergoing total hip/knee joint replacement surgery due to primary osteoarthritis (OA), and from patients with hip fractures as controls. DNA/RNA was extracted from the cartilage tissues. Real-time quantitative PCR was performed to measure gene expression, and Sequenom EpiTyper was used to assay DNA methylation. Mann-Whitney test was used to compare the methylation and expression levels between OA cases and controls. Spearman rank correlation coefficient was calculated to examine the association between the methylation and gene expression.Results. A total of 58 patients with OA (36 women, 22 men; mean age 64 ± 9 yrs) and 55 controls (43 women, 12 men; mean age 79 ± 10 yrs) were studied. SMAD3 expression was on average 83% higher in OA cartilage than in controls (p = 0.0005). No difference was observed for DNA methylation levels in the SMAD3 promoter region between OA cases and controls. No correlation was found between SMAD3 expression and promoter DNA methylation.Conclusion. Our study demonstrates that SMAD3 is significantly overexpressed in OA. This overexpression cannot be explained by DNA methylation in the promoter region. The results suggest that the transforming growth factor-β/SMAD3 pathway may be overactivated in OA cartilage and has potential in developing targeted therapies for OA.