BACKGROUND AND AIM OF THE STUDY: Sclerostin is a key negative regulator of bone 
formation. It was hypothesized that sclerostin might also play a potential role 
in the development of aortic valve calcification (AVC). The study aim was to 
evaluate serum sclerostin levels in patients with different degrees of AVC 
compared to a healthy control group, and to investigate local sclerostin 
expression in explanted calcified and non-calcified aortic valves.
METHODS: A prospective cross-sectional study was performed in 115 patients (mean 
age 74 +/- 7 years) with echocardiographically proven AVC. Sclerostin serum 
levels were measured using ELISA and compared to values obtained from a healthy 
control population. For quantification of AVC, all patients of the study cohort 
underwent non-contrast-enhanced dual-source computed tomography (DSCT). 
Immunohistochemistry (IHC) staining for sclerostin and mRNA sclerostin 
expression was analyzed in 10 calcified aortic valves and 10 non-calcified 
age-matched control valves.
RESULTS: Patients with AVC showed significantly higher sclerostin serum levels 
as compared to healthy controls (0.94 +/- 0.45 versus 0.58 +/- 0.26 ng/ml, p < 
0.001). A significant correlation between sclerostin serum levels and Agatston 
AVC scores as assessed by DSCT was observed (r = 0.62, p < 0.001) in the study 
cohort. IHC revealed positive sclerostin staining in nine calcified valves, in 
contrast to negative staining for sclerostin in all non-calcified valves. 
Quantitative real-time PCR confirmed the increased sclerostin expression on mRNA 
level, with a significant up-regulation of sclerostin mRNA (fold change 150 +/- 
52, p < 0.001) expression being shown in calcified aortic valves compared to 
non-calcified control valves. Co-staining experiments revealed that 
sclerostin-expressing cells co-express the major osteogenic transcription factor 
Runx2 and the extracellular matrix protein osteocalcin.
CONCLUSION: Patients with AVC showed increased sclerostin serum levels compared 
to a healthy reference population, and it was revealed that the severity of AVC 
may be linked to increased sclerostin serum levels. Moreover, the PCR and 
staining data demonstrated an increased sclerostin expression in parallel to 
prototypic markers of osteogenic transdifferentiation, indicating a role of 
sclerostin in the valvular calcification process.