title: High dickkopf-1 levels in sera and leukocytes from children with 21-hydroxylase deficiency on chronic glucocorticoid treatment.
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.
authors.affiliation: Dept. of Basic Medical Sciences, Neuroscience, and Sense Organs, Section of Human Anatomy and Histology, Univ. of Bari, Piazza Giulio Cesare, 11 70124 Bari, Italy. giacomina.brunetti@uniba.it
authors.forename: Giacomina
authors.initials: G
authors.lastname: Brunetti
authors.forename: Maria Felicia
authors.initials: MF
authors.lastname: Faienza
authors.forename: Laura
authors.initials: L
authors.lastname: Piacente
authors.forename: Annamaria
authors.initials: A
authors.lastname: Ventura
authors.forename: Angela
authors.initials: A
authors.lastname: Oranger
authors.forename: Claudia
authors.initials: C
authors.lastname: Carbone
authors.forename: Adriana Di
authors.initials: AD
authors.lastname: Benedetto
authors.forename: Graziana
authors.initials: G
authors.lastname: Colaianni
authors.forename: Margherita
authors.initials: M
authors.lastname: Gigante
authors.forename: Giorgio
authors.initials: G
authors.lastname: Mori
authors.forename: Loreto
authors.initials: L
authors.lastname: Gesualdo
authors.forename: Silvia
authors.initials: S
authors.lastname: Colucci
authors.forename: Luciano
authors.initials: L
authors.lastname: Cavallo
authors.forename: Maria
authors.initials: M
authors.lastname: Grano
mesh_terms: D000293:Adolescent; D000312:Adrenal Hyperplasia, Congenital / Q000097:blood* / Q000188:drug therapy*; D000469:Alkaline Phosphatase / Q000378:metabolism; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D015153:Blotting, Western; D015519:Bone Density / Q000187:drug effects / Q000235:genetics; D018801:CD2 Antigens / Q000096:biosynthesis / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D003907:Dexamethasone / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005938:Glucocorticoids / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood* / Q000235:genetics; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D018613:Microscopy, Confocal; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D053245:RANK Ligand / Q000096:biosynthesis; D060888:Real-Time Polymerase Chain Reaction; D013255:Steroid 21-Hydroxylase / Q000097:blood* / Q000235:genetics
chemical_list: D000893:Anti-Inflammatory Agents; D018801:CD2 Antigens; C501126:DKK1 protein, human; D005938:Glucocorticoids; D036341:Intercellular Signaling Peptides and Proteins; D018950:Lipopolysaccharide Receptors; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D003907:Dexamethasone; D013255:Steroid 21-Hydroxylase; D000469:Alkaline Phosphatase