ECTS2013 Poster Presentations Paediatric bone disease (7 abstracts)
High dickkopf-1 levels in sera and leukocytes from children with 21-hydroxylase deficiency on chronic glucocorticoid treatment
Giacomina Brunetti 1 , Maria Felicia Faienza 2 , Laura Piacente 2 , Annamaria Ventura 2 , Angela Oranger 1 , Claudia Carbone 1 , Adriana Di Benedetto 1 , Graziana Colaianni 1 , Giorgio Mori 3 , Silvia Colucci 1 , Luciano Cavallo 2 & Maria Grano 1
1Department of Basic Medical Sciences, Neuroscience and Sense Organs, Section of Human Anatomy and Histology, University of Bari, Bari, Italy; 2Department of Biomedical Sciences and Human Oncology, University of Bari, Bari, Italy; 3Department of Biomedical Science, University of Foggia, Foggia, Italy.
Children with 21-hydroxylase deficiency (21-OHD) need chronic glucocorticoid (cGC) therapy to replace congenital deficit of cortisol synthesis, and this therapy is the most frequent and severe form of drug-induced osteoporosis. In the study we enrolled 18 patients (9 females) and 18 sex- and age-matched controls. We found in 21-OHD patients high serum and leukocyte levels of dickkopf-1 (DKK1), a secreted antagonist of the Wnt/β-catenin signaling pathway, known to be a key regulator of bone mass. In particular, we demonstrated by flow cytometry, confocal microscopy, and real time PCR that monocytes, T lymphocytes and neutrophils from patients expressed high levels of DKK1, which may be related to the cGC therapy. In fact, we showed that dexamethasone treatment markedly induced the expression of DKK1 in a dose- and time-dependent manner in leukocytes. The serum from patients containing elevated levels of DKK1 can directly inhibit in vitro osteoblast differentiation and Receptor Activator of NF-kappaB Ligand (RANKL) expression. We also found a correlation between both DKK1 and RANKL or C-terminal telopeptides of Type I collagen serum levels in 21-OHD patients on cGC treatment. Our data indicated that DKK1, produced by leukocytes, may contribute to the alteration of bone remodeling in 21-OHD patients on cGC treatment.
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Bone Abstracts
ISSN 2052-1219 (online)
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