High dickkopf-1 levels in sera and leukocytes from children with 21-hydroxylase deficiency on chronic glucocorticoid treatment

Author:

Brunetti Giacomina1,Faienza Maria Felicia2,Piacente Laura2,Ventura Annamaria2,Oranger Angela1,Carbone Claudia1,Benedetto Adriana Di1,Colaianni Graziana1,Gigante Margherita3,Mori Giorgio3,Gesualdo Loreto4,Colucci Silvia1,Cavallo Luciano2,Grano Maria1

Affiliation:

1. Department of Basic Medical Sciences, Neuroscience, and Sense Organs, Section of Human Anatomy and Histology, University of Bari, Bari, Italy;

2. Department of Biomedical Sciences and Human Oncology, University of Bari “A. Moro”, Bari, Italy;

3. Department of Biomedical Science, University of Foggia, Foggia, Italy; and

4. Nephrology, Dialysis, and Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy

Abstract

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 this 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-κB ligand (RANKL) expression. We also found a correlation between both DKK1 and RANKL or COOH-terminal telopeptides of type I collagen (CTX) 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.

Publisher

American Physiological Society

Subject

Physiology (medical),Physiology,Endocrinology, Diabetes and Metabolism

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