title: Imbalance of osteoclastogenesis-regulating factors in patients with celiac disease.
abstract: Celiac disease is an autoimmune disorder characterized by atrophy of the intestine villi triggered by ingestion of gluten in genetically susceptible individuals. The association between celiac disease and low BMD has been recognized, but the mechanisms of disturbance are poorly understood. We show imbalance of cytokines relevant to bone metabolism in celiac patients' sera and the direct effect of these sera on in vitro bone cell activity.
  
  
  BACKGROUND
  Celiac disease is associated with mineral metabolism derangement and low BMD. We investigated whether imbalance of serum factors in celiac patients could affect human bone cell activity in vitro.
  
  
  METHODS
  We studied two groups of celiac patients--one on a gluten-free diet and another before the diet--both with decreased bone mass. Patients were investigated for bone turnover markers, and their sera were used for culturing bone cells from healthy donors and evaluate changes in cell activity.
  
  
  RESULTS
  The N-terminal telopeptide of procollagen type I and interleukin (IL)-6 were higher than normal in patients not on the gluten-free diet. IL-1beta and TNF-alpha/beta were normal in all patients. IL-12 was reduced in all patients, whereas IL-18 was reduced only in patients on the diet. The RANKL/osteoprotegerin (OPG) ratio was increased in patients not on the gluten-free diet. Persistently increased osteoclast numbers were obtained from peripheral blood mononuclear cells of healthy donors on incubation with sera of patients not on the gluten-free diet versus control sera and sera from patients on the diet. In human osteoblasts from healthy individuals, IL-18 was reduced on incubation with sera from all patients, whereas OPG expression was lower when sera from patients not on the diet were used. Proliferation, alkaline phosphatase, and nodule mineralization were increased in osteoblast cultures containing sera from all celiac patients, either on or not on the gluten-free diet.
  
  
  CONCLUSIONS
  We conclude that bone loss in celiac disease might also be caused by a cytokine imbalance directly affecting osteoclastogenesis and osteoblast activity.
authors.affiliation: Istituto Dermopatico dell'Immacolata, Istituto di Ricovero e Cura a Carattere Scientifico, Roma, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Taranta
authors.forename: Dario
authors.initials: D
authors.lastname: Fortunati
authors.forename: Maurizio
authors.initials: M
authors.lastname: Longo
authors.forename: Nadia
authors.initials: N
authors.lastname: Rucci
authors.forename: Enzo
authors.initials: E
authors.lastname: Iacomino
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Aliberti
authors.forename: Enzo
authors.initials: E
authors.lastname: Facciuto
authors.forename: Silvia
authors.initials: S
authors.lastname: Migliaccio
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Bardella
authors.forename: Antonella
authors.initials: A
authors.lastname: Dubini
authors.forename: Maria Orietta
authors.initials: MO
authors.lastname: Borghi
authors.forename: Silvia
authors.initials: S
authors.lastname: Saraifoger
authors.forename: Anna
authors.initials: A
authors.lastname: Teti
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Bianchi
mesh_terms: D000328:Adult; D000469:Alkaline Phosphatase / Q000032:analysis / Q000378:metabolism; D015415:Biomarkers / Q000097:blood / Q000378:metabolism / Q000652:urine; D015519:Bone Density; D001862:Bone Resorption / Q000209:etiology / Q000378:metabolism*; D002352:Carrier Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism; D002446:Celiac Disease / Q000150:complications / Q000378:metabolism*; D003094:Collagen / Q000652:urine; D024042:Collagen Type I; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005983:Glutens / Q000378:metabolism; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / Q000235:genetics / Q000378:metabolism; D006023:Glycoproteins / Q000097:blood / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood / Q000235:genetics / Q000378:metabolism; D010006:Osteoblasts / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism*; D053244:Osteoprotegerin; D044162:Parathyroid Hormone-Related Protein / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000652:urine; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000097:blood / Q000235:genetics / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor
chemical_list: D015415:Biomarkers; D002352:Carrier Proteins; D024042:Collagen Type I; D016207:Cytokines; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D044162:Parathyroid Hormone-Related Protein; D010455:Peptides; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; C052929:collagen type I trimeric cross-linked peptide; D005983:Glutens; D003094:Collagen; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating); D000469:Alkaline Phosphatase