Imbalance of osteoclastogenesis-regulating factors in patients with celiac disease.
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.
Taranta
Anna
A
Istituto Dermopatico dell'Immacolata, Istituto di Ricovero e Cura a Carattere Scientifico, Roma, Italy.
Fortunati
Dario
D
Longo
Maurizio
M
Rucci
Nadia
N
Iacomino
Enzo
E
Aliberti
Ferdinando
F
Facciuto
Enzo
E
Migliaccio
Silvia
S
Bardella
Maria Teresa
MT
Dubini
Antonella
A
Borghi
Maria Orietta
MO
Saraifoger
Silvia
S
Teti
Anna
A
Bianchi
Maria Luisa
ML
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
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